Isolated Frog Muscle Spindle Research Articles

Action‐potential initiation and maintained activity of the isolated frog muscle spindle

The initiation of afferent action potentials represents the basic signalling process integrating and coding information of an external stimulus. There is also evidence in sensory receptor neurons of spontaneously generating action potentials that interfere with and modify the stimulus evoked activity. The present study investigates the generation of spontaneous action potentials in the isolated muscle spindle of the frog by recording receptor potentials, small subthreshold depolarizations, propagated impulses and interspike transients from the first Ranvier-node of the afferent stem fibre. The temporal pattern of spontaneous discharges at resting length depended on several variables interacting at the encoding site. In the absence of mechanical stimulation, a large resting receptor potential steadily depolarized the encoding node and provoked action potentials at irregular intervals. After each action potential, the hyperpolarizing afterpotential provided a slowly increasing depolarizing interspike transient of decreasing slope (time constant 128 ms), which evoked small subthreshold depolarizations (decay time > 5 ms; multimodal amplitude distribution) before the following action potential discharged. The probability of the small subthreshold depolarizations increased the longer the resting receptor potential stayed constant at its maximum amplitude. When increasing the static prestretch level encoding depended also on the stretch-evoked receptor potential as an additional parameter. The resulting depolarizing interspike transients were then larger and also more steeply rising, so that the afferent discharges increased in both rate and regularity. The experiments show dynamic threshold patterns that control action-potential initiation by the assessment of the actual amplitude of depolarization and its rate of rise.

Facilitation effect of auxiliary noise stimuli on response of isolated frog muscle spindle to sinusoidal movements.

Receptor potentials and impulse patterns were recorded from isolated frog muscle spindles using sinusoidal and superimposed random stretches as stimuli with different sinus-to-noise ratios. The entire dynamic amplitude range of the spindle receptor was evaluated by measuring the sensory response at different levels of static stretch. Auxiliary random stimuli provoked rectified fast depolarizing receptor potential transients; their amplitude and slope grew larger with increasing intensity of the noise stimulus and with increasing prestretch level. Due to this strongly nonlinear behavior of the transducing site the frequency and size of the receptor potentials evoked by the auxiliary input signal increased during the stretching phase of the sinusoidal movement. Since the fast depolarizing receptor potential transients provided a powerful trigger for the action potential encoding site, auxiliary random stimuli effectively enhanced the afferent discharge rate, especially during the stretching phase of the sinusoidal movement. Auxiliary noise stimuli could even activate the afferent discharge to an otherwise subthreshold sinusoidal stretch. It is assumed that by the same mechanism the transfer characteristic of the receptor is broadened towards higher frequencies. Since auxiliary random stimuli increased the nonlinear properties of all receptor response components, a "linearizing" approximation technique only partially describes the receptor's transfer properties. The facilitation effect recorded in the differentiated muscle spindle when random stimuli were superimposed on sinusoidal displacements closely resembled the excitation of afferent firing when passive stretching interacted with active fusimotor innervation. A hypothesis is proposed to explain both effects by the same mechanism acting upon the transducing sensory endings: Since passive random stretches as well as active twitching of the intrafusal muscle fibers exhibited almost the same range of frequency components, we propose that both stimuli also generate the same kind of receptor potentials; namely, those fast-rising depolarization transients of the receptor potential, which vigorously drive the encoding site. In general, these experiments explain how the specific response of a neuron can be facilitated by an additional unspecific (noisy) input.

Encoder response of isolated frog muscle spindle elicited by pseudorandom noise stimuli.

The present experiments investigated the signal transfer in the isolated frog muscle spindle by using pseudorandom noise (PRN) as the analytical probe. In order to guarantee that the random stimulus covered the entire dynamic range of the receptor, PRN stimuli of different intensities were applied around a constant mean length, or PRN stimuli of the same intensity were used while varying the mean length of the spindle. Subthreshold receptor potentials, local responses, and propagated action potentials were recorded simultaneously from the first Ranvier node of the afferent stem fiber, thus providing detailed insight into the spike-initiating process within a sensory receptor. Relevant features of the PRN stimulus were evaluated by a preresponse averaging technique. Up to tau = 2 ms before each action potential the encoder selected a small set of steeply rising stretch transients. A second component of the preresponse stimulus ensemble (tau = 2-5 ms) opposed the overall stretch bias. Since each steeply rising stretch transient evoked a steeply rising receptor potential that guaranteed the critical slope condition of the encoding site, this stimulus profile was most effective in initiating action potentials. The dynamic range of the muscle spindle receptor extended from resting length, L0, to about L0 + 100 microns. At the lower limit (L0) the encoding membrane was depolarized to its firing level and discharged action potentials spontaneously. When random stretches larger than the upper region of the dynamic range were applied, the spindle discharged at the maximum impulse rate and displayed no depolarization block or "overstretch" phenomenon. Random stretches applied within the dynamic range evoked regular discharge patterns that were firmly coupled to the PRN. The afferent discharge rate increased, and the precision of phase-locking improved when the intensity of the PRN stimulus was increased around a constant mean stretch; or the mean prestretch level was raised to higher values while the intensity of the PRN stimulus was kept constant. In the case when the PRN stimulus covered the entire dynamic range, the temporal pattern of the afferent discharge remained constant for at least 10 consecutive sequences of PRN. A spectral analysis of the discharge patterns averaged over several sequences of PRN was employed. At the same stimulus intensity the response spectra displayed low-pass filter characteristics with a 10-dB bandwidth of 300 Hz and a high-frequency slope of -12 dB/oct. Increasing the mean intensity of the PRN stimulus or raising the prestretch level increased the response power.(ABSTRACT TRUNCATED AT 400 WORDS)

Transducer action of isolated frog muscle spindle evoked by pseudorandom noise stimuli.

The dynamic response properties of the isolated frog muscle spindle receptor were investigated by recording the receptor potential evoked by pseudorandom noise (PRN) stimuli. The entire dynamic range of the receptor was determined by measuring the sensory response either at different intensities of the PRN stimulus (sigma = 8-30 microns) around a constant mean length or at the same intensity while varying the mean length from resting length L0 up to L0 + 150 microns. The 3-dB bandwidth of the test signal was 130 Hz. Random stimuli often evoked brief receptor potentials with variable size but characteristic shape. This shape contained a fast depolarization transient of the receptor potential during the stretching phase of the stimulus and a slowly decaying repolarization transient during release of stretch. The depolarization transient rose faster in proportion to the increasing amplitude of the receptor potential, so that larger receptor potentials were more phasic in character than smaller ones. The repolarization transient exhibited two segments of different exponential decay: The first brief repolarization phase lasted for 5 ms; its decline (tau = 2-5 ms) was faster for larger receptor potentials. The second slowly decaying repolarization transient was the same for different receptor potential amplitudes (tau = 47 ms). Consequently, the slow repolarization transients of succeeding receptor potentials displayed temporal summation. Since the amplitude and shape of the receptor potential remained constant during repeated sequences of PRN stimuli, this test stimulus was the most appropriate for the investigation of dynamic response properties under stationary conditions. Long-term stimulation caused a small shift of the mean membrane voltage towards hyperpolarizing values. This finding together with the marked "off effect" after termination of the stimulus indicate the action of an electrogenic pumping mechanism. The dynamic range of the muscle spindle receptor extended from resting length L0 up to L0 + 100 microns. Within this range static prestretches placed a bias upon the transducing site and effectively enhanced the amplitude of the receptor potential. Further prestretch beyond the dynamic region kept the receptor potential constant at its maximum amplitude. The receptor potential amplitude distribution was not symmetrical about the mean but was skewed in favor of depolarization values responding to the stretch trajectories of the PRN stimulus. Variation of the operating point by increasing the static prestretch also shifted the mode of the response distribution towards depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Information transmission by isolated frog muscle spindle.

Transmission of sensory information was calculated for the isolated frog muscle spindle receptor, using Shannon's information measure. Sinusoidal movements, random noise stretches, and sinusoids with superimposed auxiliary noise were applied as stimuli. In addition, the static prestretch level of the intrafusal muscle bundle was adjusted between resting length (L0) and L0 + 600 micron, so that the analysis of the information transmission properties covered the entire dynamic range of the sensory receptor organ. Sinusoidal stretches below 2 Hz evoked smoothly modulated cycle histograms, which were approximately linearly related to the stimulating sinewave. The transinformation rates under these conditions were generally low (5-17 bit X s-1), regardless of the amplitude of the applied movement. Increasing prestretch enhanced the modulation depth of the cycle histograms considerably, but increased the transinformation rates by less than 10 bit X s-1. By contrast, sinusoids above 2 Hz evoked clearly nonlinear cycle histograms, because each action potential was firmly phase-locked to a small segment of the stretch cycle. Under these conditions the transinformation rates grew larger with increasing stimulus frequency and approached 130 bit X s-1 at 60 Hz. Small amplitude sinusoidal stretches, however, evoked considerable transinformation rates in the high frequency region only then, when the spindle receptor was extended to higher prestretch levels. Random stretches evoked transinformation rates between 5 and 30 bit X s-1 depending on both the prestretch level and the intensity of the noise stimulus. The linear response components carried only about 25% of the transinformation rates transmitted by both the linear and nonlinear response components. Auxiliary noise stimuli greatly improved the information transmission of sinusoidal stretches. For example, a pure sinusoid evoked 5 bit X s-1. Adding a noise signal with equal energy to the sinusoidal movement elicited 20 bit X s-1. This facilitation effect of auxiliary noise was restricted to low frequency sinusoidal stimuli. The present results are discussed with respect to the information transmission properties of various sensory systems evaluated by either the same or different information processing procedure as that used in the present study. The functional significance of high transinformation rates sent by the muscle spindle to the central nervous system is discussed with respect to motor control.

Action potential patterns of isolated frog muscle spindle in response to sinusoidal stimulation.

Signal transfer in the isolated frog muscle spindle is investigated using the linear frequency domain analysis technique. Sinusoidal stretches of different amplitudes (20-120 micron) and frequencies (0.1-120 Hz) were applied at different levels of static prestretch, ranging from resting length (L0) up to L0 + 400 micron, so that the frequency-response characteristics were measured at different operating points within the dynamic range. The neuronal responses were recorded from the first node of the afferent stem fiber with a modified air-gap technique. By this means, subthreshold receptor potentials, prepotentials preceding the impulse, and the propagated action potentials were recorded simultaneously, thus providing a detailed insight into the encoding process. There is a well-defined dynamic range of receptor responses. At L0, the encoding site is depolarized to its firing level and discharges spontaneous stimulus-independent impulses. The upper limit is given by the saturation of the receptor potential, which keeps the depolarization maximum below the level of sodium inactivation. Therefore a "depolarization block" or "overstretch" does not exist in the muscle spindle; i.e., the receptor retains its ability to encode information over a large range of dynamic and static displacements. Since the dynamic curves of the receptor potential are not symmetrical about their static operating point, the impulse pattern remains modulated throughout the dynamic range, even if small sinusoids are superimposed on a large static prestretch. The afferent discharge pattern is mainly regulated by the modulated AC component of the receptor potential. At low stimulus frequencies (less than 1 Hz) the receptor potential modulates almost linearly about the mean membrane voltage, so that the evoked discharge pattern displays a smooth analog signal, which is close to sinusoidal. Increasing the static prestretch increases both the peak response and the modulation depth of the impulse pattern. In the intermediate frequency range (1-10 Hz), the cycle histogram disintegrates into discrete peaks separated by empty bins, because the nonlinear receptor potential elicites firmly phase-locked action potentials during its fast depolarization transient. Raising the prestretch level improves the precision of phase locking and increases the number of spikes elicited per cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Receptor potentials of isolated frog muscle spindle evoked by sinusoidal stimulation.

Receptor potentials in response to sinusoidal stimulation have been recorded from isolated muscle spindles of the frog. Sinusoidal displacements of different amplitudes (20-120 micron) and frequencies (0.1-100 Hz) were used. The mean static stretch level was adjusted between resting length (L0) and L0 + 400 micron, so that the amplitude and phase-response characteristics were measured at different operating points. Depending on the amount of static prestretch, there is a well-defined dynamic range, which limits the receptor potential by nonlinear compression of either its positive or negative half-cycle. For each point on the static operating curve there exists a dynamic operating curve with a sigmoidal shape. The range of each dynamic curve is approximately 80 micron, independent of the static displacement, and the maxima of all dynamic curves are the same. Therefore the dynamic curves are not symmetrical about their static operating point. The slope of the steepest portion is 10% of the maximum elicitable receptor potential per 10-micron dynamic displacement. For stimulus frequencies greater than 2 Hz the receptor potential deviates from a sinusoidal waveform, exhibiting a fast depolarization transient during stretch and a prolonged repolarization transient during release of stretch. The steepness of the depolarization transient increases with increasing stimulus frequency, amplitude, and prestretch level. As a result, the interval from trough to peak of the receptor potential shortens to less than 90 degrees instead of half a cycle. The repolarization transient has an exponential decay with a time constant of approximately 40 ms that remains constant during the various stimulus conditions. As a result of this slow decay time, individual receptor potentials summate, so that the response divides into a modulated receptor potential (AC component) and a maintained depolarization (DC component). The amplitude response characteristic of the stationary AC component increases with increasing stimulus frequencies up to a peak at 2 Hz, after which it declines with a slope of -3 dB/octave. Provided large sinusoidal stretches and/or extended prestretch levels are used, this high-frequency decline of the AC component is compensated for by the proportional increase of the DC component, so that the peak depolarization values remain constant from 2 to 100 Hz. Stimulus and response are in phase for stimulus frequencies less than 2 Hz and reverse to phase lag at higher stimulus frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)

The transducer and encoder of frog muscle spindles are essentially nonlinear. Physiological conclusions from a white-noise analysis.

Nonlinear second order white-noise analysis has been applied to the isolated frog muscle spindle. Power (delta 2) of the Gaussian white noise (GWN) and the average prestretch level L were varied and the response of both the isolated receptor potential (transducer) and the action potential (encoder) level were analysed. The standard white-noise method is briefly presented. Particular emphasis, however, is put on the limitations in the range of validity of the method and, consequently, on the use and interpretation of the kernels as a Wiener model. Conclusions in the present paper are within this frame and are mainly of qualitative nature. The analysis reveals that the nonlinear contributions of the model are essential for approximating physiological results, thus ruling out purely linear modelling for this receptor organ. The dependence of the transducer kernels on delta are compatible with the behaviour of a rectifier. Rectification is represented by the lack of hyperpolarization within the isolated receptor potential and is enhanced by the substantial memory in the linear and nonlinear kernels as demonstrated by their extent in time. This is equivalent to low power in high frequencies of the response. Obviously, the hyperpolarizing potentials following each spike counteract the long transducer memory. At the encoder level the memory of the system is strongly reduced. This is achieved by using predominantly high frequency components of the receptor potential for triggering the process of impulse generation, and by the precise coupling and high frequency content of the impulses. This coupling precision is possible because of the sensitivity of the spike-generating mechanism to steep rising transients of the receptor potential and also owing to the reduction in transducer memory by the hyperpolarizing afterpotentials. The preference given to the high frequency components is also read from the structure of the second order transducer kernel and from both the linear and the second order encoder kernels, which allows the most effective input waveform for triggering action potentials to be determined. When the operating point is changed to higher prestretch values, kernel heights increase strongly implying higher response strength of the muscle spindle.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of adequate stimulation on the discharge pattern of an isolated frog muscle spindle

Discharges from an isolated frog muscle spindle during mechanical stimulation of varied amplitude, velocity, and shape were investigated. The firing rate during a linear increase in strength of the stimulus is determined by its amplitude, whereas the change in firing rate is determined by the rate of increase of amplitude. With sinusoidal stimulation the firing rate apparently reproduces stimulus shape, i.e., the muscle spindle is sensitive not only to amplitude and velocity, but also to acceleration of the stimulus. Sensitivity to acceleration is most probably due to the change in threshold of appearance of action potentials observed during variation of the speed of stretching.

Effect of hypertonic solutions on electrical activity of the isolated frog muscle spindle

Changes in electrical activity of the isolated frog muscle spindle were investigated in hypertonic solutions obtained by adding 400 mM sucrose, glucose, or glycerol to Ringer's solution. The spontaneous firing rate in hypertonic sucrose and glucose solutions increased at first (for 3–5 min) and then fell rapidly to zero; the receptor potential and evoked spike activity diminished under these conditions and disappeared. In the hypertonic solution with glycerol a similar effect was observed but, unlike in the first two media, in this case spike activity returned after its initial increase to the normal level; a second rise in the firing rate was then observed up to a steady value which was higher than normal. After rinsing out the hypertonic sucrose and glucose solutions with ordinary Ringer's solution the spontaneous and evoked activity gradually returned to normal with a small overshoot. During the rinsing out of the hypertonic glycerol solution a sharp and considerable rise in spontaneous activity was first observed, while the changes in frequency of the evoked activity were negligible. The spike activity then returned to normal. The observed changes in electrical activity of the muscle spindle in hypertonic media are attributed to deformation of the sensory terminals and intrafusal muscle fibers (in the glycerol medium), leading to depolarization of the receptor membrane.

Effect of pH and calcium of the surrounding medium on electrical activity of the isolated muscle spindle

The effect of pH and the calcium ions of the surrounding medium on the receptor potential and unit activity of the isolated frog muscle spindle was investigated. With a decrease in pH of the medium the amplitude and duration of the hyperpolarization phase of the receptor potential increased and the amplitude of its depolarization phase decreased. The frequencies of the spontaneous and evoked activity were reversibly reduced under these conditions. A change in pH of the surrounding medium toward the alkaline side led to a decrease in the amplitude and duration of the hyperpolarization phase of the receptor potential. The firing rate initially increased and then decreased to 30–50% of normal. An increase in the calcium concentration in an alkaline medium led to an increase, but in an acid and normal medium to a decrease, in firing rate. The observed changes in electrical activity of the muscle spindle in solutions can be explained by changes in the velocity of active (electrogenic) and passive transport of sodium and calcium ions.

Role of active ion transport in reception of the generator potential of the isolated frog muscle spindle

The effect of complete replacement of sodium ions by lithium ions in Ringer's solution and of 10−4 M ouabain on the receptor potential of the isolated frog muscle spindle was investigated. Initially, under the influence of lithium ions and ouabain, the hyperpolarization phase of this potential diminished and disappeared, and later the same fate befell the static and dynamic part of its depolarization phase. The rise time of the receptor potential was increased in a solution containing lithium ions but in the solution with ouabain it remained the same as initially. No appreciable changes were found in the rate of fall of the dynamic part of the depolarization phase. On rinsing the muscle spindle in normal Ringer's solution in the experiment with lithium ions recovery was incomplete, and in the experiments with ouabain the receptor responses were not restored.

Response of Isolated Frog Muscle Spindle to Sine Wave Stimulation

AbstractThe impulse response and the receptor potential 01 the isolated muscle spindle of the frog were recorded during sinusoidal stretching at frequencies from 0.1 c/s to 100 c/s. Attention was focused on the changes of the responses in the initial phase of stimulation before the steady state was reached. In the course of sine wave stimulation the impulse response of the spindle undergoes regular changes characterized by an increase in threshold and latency of the individual impulses, a decrease in phase lead and peak frequency and a reduction in number of spikes in each cycle. The changes are most pronounced during the first 2–5 cycles, and a steady state with a fixed impulse patterning is usually reached after 10–15 cycles. The receptor potential evoked by a sine wave stretch is distorted in comparison with the waveform of the stimulus in having a relatively faster rise and slower decay. With changes in frequency and amplitude of stimulation it undergoes characteristic alterations in phase lead and configuration. When superimposed upon a constant stretch or a linearly rising stretch, sinusoidal stimulation produces responses which increase in amplitude with the underlying stretch. These observations provide evidence that the sensory endings responsible for the transducer action do not obey linear transfer functions.

Effect of a polarizing current on receptor potential of the isolated frog muscle spindle

The effect of a polarizing current on electrical activity of the isolated frog muscle spindle was studied. A depolarizing current increased the frequency and reduced the amplitude of afferent spike activity, both spontaneous and evoked by mechanical stimulation. A hyperpolarizing current produced the opposite effect. The amplitude of the receptor potential in response to a mechanical stimulus varied as a linear function of the intensity of the polarizing current

Effect of ouabain on electrical activity of the isolated frog muscle spindle

Changes in electrical activity of the isolated frog muscle spindle were studied in Ringer's solution containing ouabain. The presence of ouabain in the solution increased the spontaneous firing rate of the receptors up to a maximum and then reduced it quickly to zero. The amplitude of the action potentials was reduced on the average to 40% of normal. Ouabain causes initial disappearance of the hyperpolarization phase of the receptor potential and a subsequent decrease in amplitude of its dynamic phase to zero. The decrease in amplitude of the receptor potential and action potential and also the changes in firing rate in the solution with ouabain depend on the frequency of their spontaneous activity. The changes observed can be explained by depolarization of the membrane of the nerve endings and the first node of Ranvier, developing as a result of blocking of the sodium pump by ouabain.

Effect of tetraethylammonium ions on electrical activity of the isolated frog muscle spindle

Changes in electrical activity of the isolated frog muscle spindle in Ringer's solution containing tetraethylammonium (TEA) ions were studied. An increase in the frequency of spontaneour activity was observed, but with continued perfusion with TEA solution both spontaneous afferent impulses and action potentials generated during stretching of the muscle receptor were blocked. The dynamic component of the depolarization phase of the receptor potential was reduced in amplitude and increased in duration. Rinsing the receptor in normal physiological saline did not restore its responses completely.

Effects of tetrodotoxin on responses of the frog muscle spindle.

Effects of tetrodotoxin on the spindle potential and the spike of isolated frog muscle spindle recorded using the paraffin gap method were studied.2×10-8g/ml toxin first abolished the conductive spike and subsequently reduced the amplitude and the rate of rise of the abortive spike or the prepotential. 5×10-8g/ml or more toxin erased the abortive spike and the prepotential without producing any significant effect on the spindle potential.It is assumed from the results that the prepotential may be the same as the abortive spike, and that the abortive spike may play a primary role in the initiation of the conductive spike as the prepotential when its amplitude is higher than a trigger level.The spindle potential was modified greatly depending on the sideward displacement of the axon in the paraffin pool during muscle stretch. Consequently, it seems that a part of the spindle potential may consist of an artifact.

Relation between tension and sensory response of the isolated frog muscle spindle during stretch.

AbstractThe tension developed in the isolated frog muscle spindle during stretch has been studied and related to the impulse response and the isolated receptor potential of the spindle. With a steplike stretch tension rose to an initial peak and then declined towards a steady level. The decay consisted of an initial phase of rapid fall and a later phase of slow decline when stretch was prolonged. The magnitude of the peak and the static level of tension were exponential functions of the amount of stretch. The response of the spindle in terms of the impulse discharge and the isolated receptor potential closely followed the tension changes during various phases of stretch. Adaptation of the spindle to maintained stretch, in terms of the fall of the receptor potential, followed the same general time course as the decay in tension. The results suggest that tension during stretch reflects structural changes within the spindle and that these changes may bear a more direct relation to the sensory response than lengthening. Neither the gross tension nor the elongation ran, however, be regarded as a dirert representation of the actual stimulus to the endings.

Length changes within isolated frog muscle spindle during and after stretching.

1. The length changes within the frog muscle spindle during stretch have been studied by stroboscopic photomicroscopy. Attention was focused on the length changes within the central reticular zone and these changes were related to the features of the receptor potential.2. It was found that the length changes of the central reticular zone closely followed the applied stretch in time course and magnitude. The results suggest that the length changes of the polar zones are generally similar to those in the central zone.3. There was no evidence of a relative shortening of the central zone in the early phase of maintained stretch, corresponding to the decline of the receptor potential from its dynamic peak to the static level.4. Following release of stretch the central zone returned to its original resting length within a few msec. The rapid return of the spindle was in sharp contrast to the relatively slow exponential decay of the receptor potential. With strong or prolonged stretches the return became slower and resting length was not completely restored until 100-150 msec after release of stretch. No corresponding change in the decay of the receptor potential was seen.5. The results suggest that the early adaptive fall of the receptor potential is not related to differential length changes between the central zone and the polar zones. It seems more likely that the contribution of mechanical factors to the early adaptation of the frog spindle have to be sought at the ultrastructural level.6. The finding that the length changes closely follow the applied stretch suggests that the stimulus in terms of lengthening is transmitted to the endings with little distortion.7. The results suggest that the elastic elements play a dominant role for the transmission of the stimulus to the endings and for the return of the spindle to resting length after release of stretch.

The action of tetrodotoxin on the frog's isolated muscle spindle.

AbstractTetrodotoxin in concentrations of 0.8–1.0 × 10‐7 g/ml completely blocked conducted activity of the afferent nerve of isolated frog muscle spindle without affecting the receptor potential. Development of block was characterized by an increase in threshold of the nerve, a gradual delay of the onset of the impulse response and a reduction and decomposition of the individual action potentials into smaller spikes. The spike decomposition appeared to be due to a de‐synchronization of the conducted activity in the branched afferent terminals. After block by tetrodotoxin for up to 20 min the normal response could be restored by washing the preparation with Ringer's solution. The blocking action of tetrodotoxin was delayed and reduced by increasing calcium; removal of calcium had the opposite effect. Tetrodotoxin (1000 ng/ml) had no significant effect on the receptor potential. With low sodium plus tetrodotoxin the receptor potential was reduced by about 50 %; this reduction was reversed by addition of normal sodium. It is suggested that the sodium carrying system of the generator potential differs from that underlying the regenerative activity.