Action Potential Rate Of Rise Research Articles

Reversal of the late phase of spike frequency adaptation in cat spinal motoneurons during fictive locomotion.

In spinal motoneurons, late spike frequency adaptation (SFA) is defined as the slowing of the firing rate over tens of seconds and can be seen during sustained or intermittent current injection. Although the function of late SFA is not known, it may result in a decrease in force production over time, or muscle fatigue. Because locomotion can persist for long periods of time without fatigue, late SFA was studied using intracellular recordings from adult cat motoneurons during fictive locomotion. Of eight lumbar motoneurons studied, all showed late adaptation during control conditions, but none demonstrated late adaptation during locomotor activity. The most consistent properties that correlated with the presence or absence of late SFA were those related to availability of fast, inactivating sodium channels, particularly action potential rate of rise. Evidence of the reversal of late SFA during locomotion was present for several minutes following locomotor trials, consistent with the suggestion that SFA is modulated through slow metabotropic pathways. The abolition of late adaptation in spinal motoneurons during fictive locomotion is an example of a state-dependent change in the "intrinsic" properties of mammalian motoneurons. This change contributes to increased excitability of motoneurons during locomotion and results in robust firing during sustained locomotion.

Sodium channel slow inactivation and the distribution of sodium channels on skeletal muscle fibres enable the performance properties of different skeletal muscle fibre types.

Na+ currents (INa) and membrane capacitance were studied with the loose patch voltage clamp technique and action potential properties were studied with a two-electrode voltage clamp on the end-plate, at the end-plate border and on extrajunctional membrane of skeletal muscle fibres. Slow inactivation regulates the available INa and is operative at the resting potential of both rat and human fibres. At the resting potential, slow inactivation causes a greater reduction in INa in fast-than in slow-twitch fibres. The relative resistance of slow-twitch fibres to slow inactivation may enable slow-twitch fibres to remain tonically active. Na+ channel inactivation may provide a peripheral mechanism that limits the duration that fast-twitch fibres can fire at high rates to prevent injury associated with prolonged high-frequency contraction. Consequently, slow inactivation may enable fast-twitch fibres to operate phasically at high rates or slow-twitch fibres to fire continuously at lower rates. For both fast- and slow-twitch fibres. INa normalized to membrane area was greatest on the end-plate, intermediate on the end-plate border and smallest on extrajunctional membrane. When normalized to membrane capacitance. INa was the same on the end-plate and the end-plate border and smallest on extrajunctional membrane. For a given membrane region, INa was larger on fast- than on slow-twitch fibres. The higher density of Na+ channels near the end-plate increased the safety factor for neuromuscular transmission by lowering the action potential threshold and increasing the action potential rate of rise at the end-plate.

The effects of exposure to exogenous fatty acids and membrane fatty acid modification on the electrical properties of NG108-15 cells.

The role of membrane lipid composition in determining the electrical properties of neuronal cells was investigated by altering the available fatty acids in the growth medium of cultured neuroblastoma X glioma hybrid cells, clone NG108-15. Growth of the cells for several days in the presence of polyunsaturated fatty acids (linoleic, linolenic, and arachidonic) caused a pronounced decrease in the Na+ action-potential rate of rise (dV/dt) and smaller decreases in the amplitude, measured by intracellular recording. Oleic acid had no effect on the action potentials generated by the cells. In contrast, a saturated fatty acid (palmitate) and a trans monounsaturated fatty acid (elaidate) caused increases in both the rate of rise and the amplitude. No changes in the resting membrane potentials or Ca2+ action potentials of fatty acid-treated cells were observed. The membrane capacitance and time constant were not altered by exposure to arachidonate, oleate, or elaidate, whereas arachidonate caused a small increase in membrane resistance. Examination of the membrane phospholipid fatty acid composition of cells grown with various fatty acids revealed no consistent alterations which could explain these results. To examine the mechanism for arachidonate-induced decreases in dV/dt, the binding of 3H-saxitoxin (known to interact with voltage-sensitive Na+) channels was measured. Membranes from cells grown with arachidonate contained fewer saxitoxin binding sites, suggesting fewer Na+ channels in these cells. We conclude that conditions which lead to major changes in the membrane fatty acid composition have no effect on the resting membrane potential, membrane capacitance, time constant, or Ca2+ action potentials in NG108-15 cells. Membrane resistance also does not appear to be very sensitive to membrane fatty acid composition. However, changes in the availability of fatty acids and/or changes in the subsequent membrane fatty acid composition lead to altered Na+ action potentials. The primary mechanism for this alteration appears to be through changes in the number of Na+ channels in the cells.

Early electrophysiologic and anatomic alterations in cat ventricular muscle after coronary artery ligation.

The effect of coronary artery ligation on electrophysiologic properties of cat ventricular muscle cells was studied. Depression of resting potential, action potential rate of rise and amplitude was observed in infarcted cells, 30 min to 5 days after ligation. Action potential duration was markedly shortened in acute stages (30-120 min) but gradually lengthened to above control by 48 h. Anatomic sequelae included oedema, loss of fibre striation and cellular necrosis.

Electrophysiologic effects of encainide (MJ 9067) on canine purkinje fibres

Microelectrodes were used to characterize the actions of a new antiarrhythmic compound, encainide, 4-methoxy-2′-[2-(1-methyl-2-piperidyl)-ethyl] benzanilide, on transmembrane potentials generated by isolated canine Purkinje fibres in tissue bath. Encainide, 1×10 −7 M, had no effect on resting potential (RP) and action potential (AP) of stimulated fibres or automaticity of spontaneously fibres. Encainide (1×10 −6 M) shortened phase 2 and action potential duration (APD) at 50, 75 and 100% of repolarization; AP rate of rise (V̇max) decreased only ∼15% at 3 h exposure, while RP was unchanged. Higher concentrations also shortened phase 2 and APD, markedly decreased V̇mac, depressed the membrane responsiveness curve and increased conduction time. Encainide, 1×10 −6 M, increased ERP/APD 100. These effects were rapidly reversed by washing with drug-free solution. Encainide (1×10 −5 M) decreased the automatic rate of spontaneously beating untreated fibres and stretch-depolarized fibres, but had little effect on catecholamine-enhanced automaticity. Encainide, 1×10 −5 M, delayed the onset of ouabain toxicity. These findings suggesting that the antiarrhythmic effect of encainide may arise from its depression of V̇max and memrane responsiveness, increase in ERP/APD 100 and inhibition of automaticity, are discussed in light of the similarity of the actions of this new drug to the known properties of lidocaine and quinidone.

Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non-specific and opiate drug receptor mediated blockade.

The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro-electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0-35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60-90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(-5) to 3 X 10(-4) mM) at 70-90 min blocked the second phase of the meperidine-induced depression. 4. With lower concentrations of meperidine (0-18 and 0-07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1-5 X 10(-2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non-specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.

The electrophysiologic effects of low and high digoxin concentrations on isolated mammalian cardiac tissue: reversal by digoxin-specific antibody.

The effects of digoxin on electrophysiologic properties were evaluated in isolated perfused cardiac tissue. In canine Purkinje fiber (PF)-ventricular muscle (VM) preparations, control measurements, using microelectrode technique, were made of: resting potential (RP), action potential (AP) amplitude, rate of rise, overshoot, duration (APD), membrane responsiveness, conduction velocity (CV), and refractory period. The preparation was then exposed to 1 x 10(-7) M digoxin and repeat measurements were carried out every 15 min. At slow (30/min) rates of stimulation APD initially prolonged then markedly shortened. With more rapid stimulation (75 and 120/min) no initial APD prolongation was observed. When stimulated at 75/min, RP and AP rate of rise, amplitude, and CV remained near control values for 60-75 min then rapidly decreased until electrical inexcitability (110+/-15 min). At that time fibers were perfused with serum containing digoxin-specific antibody (DSA) or one of a group of test solutions. In the preparations exposed to DSA, membrane characteristics improved by 15 min, and by 60 min approximated control values. No beneficial effect was seen with the various test solutions. DSA also reversed digoxin-induced enhanced phase 4 depolarization in PF. Effective (ERP) and Functional (FRP) refractory periods of rabbit atrioventricular (AV) node preparations were measured in the control state. The tissue was then exposed to 1 x 10(-7) M digoxin and refractory period measurements repeated. At a time when AV conduction prolonged by 20%, associated with marked prolongation of ERP and FRP, DSA or various test solutions were perfused. The prolongation in ERP, FRP, and AV conduction time rapidly returned to normal only in the DSA perfused tissue. It is concluded that DSA has the ability to reverse pronounced toxic electrophysiological effects of digoxin in in vitro cardiac tissue.

B a2+ and S r2+ reversal of the inhibition produced by ouabain and local anesthetics on membrane potentials of cultured heart cells

Ouabain (10 −6−10 −3 M) produced only inhibitory effects on the electrical activity of cultured chick heart cells; partial depolarization and depression of the action potential rate of rise gradually occurred leading to eventual cessation of firing. Cocaine and tetracaine produced depolarization and inhibitory effects similar to those of ouabain. The depressed electrical activity and quiescence induced by these drugs was rapidly reversed by Sr 2+ or Ba 2+ (5–10 m M), which usually produced a large hyperpolarization before the onset of the reversal of inhibition. As previously reported, Ba 2+ and Sr 2+ (5–10 m M) rapidly converted quiescent nonpacemaker cells into pacemakers; Ba 2+ increased membrane resistance (presumably by decreasing K + conductance) and produced partial depolarization, whereas Sr 2+ always hyperpolarized. With lowering of [Na +] 0 below 50 m M using Li + or sucrose replacement, the action potential rate of rise became progressively depressed, the overshoot usually diminished, and firing eventually ceased, whereas the resting potential was only slightly affected; thus the inward current during an action potential seems to be normally carried by Na +. The lack of a hyperexcitable effect of ouabain is consistent with the hypothesis that catecholamine release is necessary for such action. The depolarization produced by ouabain and the local anesthetics may be due to inhibition of active ion transport. The rapid hyperpolarization produced by Ba 2+ and Sr 2+ in the presence of ouabain, cocaine and tetracaine could be due to a change in conductance or to stimulation of the Na + pump.