Adapting Lobster Stretch Receptor Neurone Research Articles

Properties of an A-current in slowly and rapidly adapting stretch receptor neurones of lobster

A previously unnoticed outward membrane current has been identified, characterized and specified as a so-called A-current in the slowly and rapidly adapting lobster stretch receptor neurone. In both cells the current was, after blockage of a tetrodotoxin-sensitive Na + current and a tetraethylammonium- and 4-aminopyridine-sensitive delayed rectifier current, seen to activate fully within about 25 ms of square-shaped depolarizations beyond voltage levels of -40 to -30 mV and, then, to inactivate completely with a (voltage independent, within the voltage span under observation) time constant of 110 ms. The A-currents of rapidly and slowly adapting receptors were noticed to differ significantly from each other in that the A-current of the rapidly adapting cell is activated, and inactivated, at 10-15 mV more negative voltage levels than the A-current of the slowly adapting cell. Also, the maximum permeability of the A-channel system appeared to be distinctly larger in the rapidly than in the slowly adapting cell. Both of these circumstances were able to explain why, at a given level of membrane depolarization, a markedly stronger A-current is activated in the rapidly than in the slowly adapting cell. On the basis of experimental data it was possible to formulate a mathematical A-current description which was incorporated into a previously published model of the lobster stretch receptor neurone. Using this model, evidence was obtained that the A-current may play a functionally significant role (in the rapidly adapting cell) by increasing the speed of action potential repolarization and thereby enhancing the cell's dynamic stimulus sensitivity.

Functional effects of a hyperpolarization-activated membrane current in the lobster stretch receptor neurone.

The functional effects of a hyperpolarization-activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than -65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around -75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mM Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post-tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 degrees C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na-K pump.

Ion (H+, Ca2+, Co2+) and temperature effects on a hyperpolarization‐activated membrane current in the lobster stretch rceptor neurone

The effects of some ions (H+, Ca2+, Co2+) and temperature on the Q-channel (a channel which conducts a hyperpolarization-activated membrane current, IQ) was investigated in the slowly adapting lobster stretch receptor neurone. It was found: (1) that increases in pH cause an increase in the maximum channel conductance; (2) that Co2+ (1 mM) and increases in extracellular Ca2+ produce a positive shift of the relationship between the membrane voltage and the steady-state channel activation along the voltage scale; (3) that Co2+ and decreases in extracellular pH cause a decrease in rate of the voltage-dependent step of the channel's gating reaction; (4) that none of the ions has an effect on the rate of the voltage-independent step of the gating reaction; and (5) that Co2+ and K+ do not interfere with each other's actions on the channel's gating reaction and maximum ion conductivity. Increases in temperature from 13 to 23 degrees C were found: (1) to cause an increase in the maximum Q-channel conductance by a factor of 1.7; (2) to have no effect on the voltage dependence of the channel's gating reaction; but (3) to lead to an increase in rate of the gating reaction by a factor of about five for the voltage-dependent, and by a factor of about three for the voltage-independent gating step. The temperature sensitivity of the IQ mechanism proved to be mathematically reproducible by a previously developed, and slightly modified Q-channel model (Edman et al. 1987, Edman & Grampp 1989), and to be of no significance in the control of membrane excitability in a thermally unstable environment.

Current activation by membrane hyperpolarization in the slowly adapting lobster stretch receptor neurone.

1. A polarization-induced membrane current, IQ, was investigated in the slowly adapting lobster stretch receptor neurone using conventional electrophysiological techniques including intracellular ion measurements. 2. The current was readily blocked by Cs+ in a voltage-dependent manner, but proved to be unaffected by tetrodotoxin, tetraethylammonium and 4-aminopyridine. 3. From an analysis of the ionic basis of IQ, it appeared that the current is carried by both Na+ and K+ through a membrane channel whose permeability for K+ is about six times larger than that for Na+ in a normal ionic environment. In the presence of reduced external Na+ concentration the Q-channel increases its permeability for both Na+ and K+, but more so for Na+ than for K+. 4. Kinetically, IQ was found to be characterized by a steep sigmoidal relationship between membrane voltage and steady-state current activation, and by a bell-shaped relationship between membrane voltage and the time constant of the exponential phase of current activation or deactivation. A significant feature of the latter relationship is a tendency to level off at finite time-constant values in both strongly hyperpolarizing and strongly depolarizing voltage regions. 5. From the experiments a mathematical IQ model was inferred. This model was based on constant-field and channel-gating kinetics involving a voltage-dependent reaction step in series with a voltage-independent reaction step. The model was found to successfully reproduce IQ behaviour in the living preparation. 6. Functionally, the activation of IQ was found to play a role in setting the cell's resting polarization and membrane excitability. This function was inferred from experiments on unimpaled cells in which it was possible to demonstrate some overlap between the voltage ranges of IQ activation and impulse initiation. In addition, in impaled cells the activation of IQ was found to cause some shortening of post-tetanic membrane hyperpolarization and to accelerate, thereby, the post-tetanic restoration of membrane excitability to control levels.

Analysis of gated membrane currents and mechanisms of firing control in the rapidly adapting lobster stretch receptor neurone.

1. The gated membrane currents (a tetrodotoxin-sensitive Na+ current and a tetraethylammonium- and 4-aminopyridine-sensitive K+ current) of the rapidly adapting stretch receptor neurone of lobster were investigated with respect to their kinetic properties using electrophysiological, pharmacological, and mathematical techniques. 2. The currents were found to be controlled by slow inactivations as well as by fast Hodgkin-Huxley (1952) gating processes. They could be described by kinetic expressions which differed from those inferred for the slowly adapting receptor (Gestrelius & Grampp, 1983a; Gestrelius, Grampp & Sjölin, 1983) only with respect to some of the parameter values. 3. With these expressions, and additional equations for the cell's pump and leak current components (Edman, Gestrelius & Grampp, 1986), a mathematical receptor model was formulated which accurately predicts the impulse activity of the living preparation in different functional circumstances and which, therefore, was adopted as an appropriate theory of firing regulation. 4. From a model analysis it appeared (a) that the 'rapid' adaptation of the receptor's impulse activity is mainly an effect of slow Na+ current inactivation starting a regenerative process of accommodation which, basically, is due to a small ratio of subthreshold Na+ to K+ currents; (b) that, because of the transmembrane Na+ influx being limited by accommodation, impulse firing is only little affected by a Na+-dependent pump current activation; and (c) that the phenomenon of increased firing frequency initially during prolonged stimulation ('negative adaptation') is an effect of the slow K+ current inactivation being faster than the slow Na+ current inactivation at comparable degrees of membrane polarization. 5. From further model studies it also appeared that, during depolarizations between successive action potentials evoked by constant stimulation, the membrane behaves like a high-resistance constant-current generator feeding into a short-circuiting capacitor. In consequence, the cell's stimulus sensitivity (change in firing frequency with stimulation strength) is, at functionally relevant stimulation intensities, mainly determined by the membrane capacitance and by the amplitude of the interspike membrane depolarization while, at higher stimulation intensities and firing frequencies, it becomes more and more a function of the spike duration itself.

Impulse firing in the slowly adapting stretch receptor neurone of lobster and its numerical simulation.

A mathematical model of the electrical activity of the slowly adapting lobster stretch receptor neurone is presented. The model is based on constant field and state transition theory and employs measurements of the kinetics of membrane currents in sub- and near-threshold voltage regions (Gestrelius, Grammp & Sjölin 1981, Gestrelius & Grampp 1983, Gestrelius, Grampp & Sjölin 1983, Edman, Gestrelius & Grampp 1983). In addition to the classical action potential generating mechanisms (Hodgkin & Huxley 1952) the model also includes the processes of slow Na and K inactivation, ion flux dependent changes of the intracellular Na+ and K+ concentrations, and the activity of an electrogenic Na-K pump sensitive to intracellular Na+ accumulation. The model is able to correctly simulate recorded action potentials as well as repetitive firing both with respect to stimulus dependence (sensitivity) and time dependence (adaptation) during prolonged electrical stimulation. In the living cell firing adaptation is found to consist of an initial phase with a relatively high, and a later phase with a lower rate of adaptation. From the model properties it can be concluded that the initial phase is mainly caused by the slow Na inactivation, while the later phase is due to a slow Na+ influx dependent pump current activation.

Kinetics of the TTX sensitive Na+ current in the slowly adapting lobster stretch receptor neurone.

The kinetics of the TTX sensitive Na+ current (INa) in the slowly adapting lobster stretch receptor neurone were investigated in sub- and near-threshold voltage regions using electrophysiological and pharmacological techniques. In dynamic conditions INa was found to display both fast and slow reactions. These were attributed to a fast Hodgkin-Huxley type of Na activation and inactivation, and a slow type of Na inactivation, respectively. In stationary conditions the voltage dependence of the slow Na inactivation was shifted in a depolarizing direction by increasing, and in a hyperpolarizing direction by decreasing the extracellular Ca++ concentration. From this finding as well as from its kinetic properties the slow Na inactivation was classified as a genuine gating process. The processes of fast Na activation and inactivation were too fast for a dynamic analysis with the recording technique available. An estimate of their stationary voltage dependence could however be obtained in a voltage range from about -80 to about -50 mV. The experimental findings were used for the formulation of a mathematical description of INa in the present preparation based on constant field and state transition theories.

Kinetics of the TEA and 4-AP sensitive K+ current in the slowly adapting lobster stretch receptor neurone.

The kinetics of the TEA and 4-AP sensitive K+ current (IK) in the slowly adapting lobster stretch receptor neurone were investigated in sub- and near-threshold voltage regions using electrophysiological and pharmacological techniques. In dynamic conditions IK was found to display both fast and slow reactions. These were attributed to a Hodgkin-Huxley type of K activation, and a slow type of K inactivation, respectively. The slow K inactivation could be shown to be unrelated to K+ flux dependent changes in intra- and pericellular K+ concentrations. Its stationary voltage dependence was however shifted in a depolarizing direction by increasing, and in hyperpolarizing direction by decreasing the extracellular Ca++ concentration. In view of these findings, and of its kinetic properties, the slow K inactivation was classified as a genuine channel gating process. The process of K activation was too fast for a dynamic analysis with the recording technique available. An estimate of its stationary voltage dependence could however be obtained in a voltage range from about -100 to about -40 mV. The experimental observations were utilized in the formulation of a mathematical model describing the kinetic behaviour of IK in the present preparation based on constant field and state transition theories.