The relation of Vmax to INa, GNa, and h infinity in a model of the cardiac Purkinje fiber

Abstract

The inward sodium current in cardiac muscle is difficult to study by voltage clamp methods, so various indirect experimental measures have been used to obtain insight into its characteristics. These methods depend on the relationship between maximal upstroke velocity of the action potential (Vmax) and the sodium current (INa), usually defined in terms of the Hodgkin-Huxley model. These relationships were explored using an adaptation of this model to cardiac Purkinje fibers. In general Vmax corresponded to INa, and it could be used to determine the relationship of membrane potential to GNa, and h infinity. The results, however, depended on the method of stimulation of the action potential, and an optimal stimulation method was determined. A commonly used experimental technique called "membrane responsiveness" was shown to distort seriously the properties of steady-state gating inactivation that is supposed to measure. Estimation of the changes in maximal sodium conductance, such as those produced by tetrodotoxin (TTX), would be accurately measured. Some experimental results have indicated a voltage-dependent effect of TTX. Characteristics of the measures of TTX effect under those conditions were illustrated. In summary, calculations with a model of the cardiac Purkinje fiber action potential provide insight into the accuracy of certain experimental methods using maximal upstroke velocity as a measure of INa, and cast doubt on other experimental methods, such as membrane responsiveness.

Resting, and rate‐dependent depression of of guinea‐pig ventricular action potentials by amiodarone and desethylamiodarone

“…Preparations were allowed to equilibrate for 2 to 3 h before taking recordings. During this time and throughout the experiment, they were driven from bipolar platinum electrodes providing rectangular pulses of sufficient amplitude to limit variations in latency (between stimulus and action potential upstroke) to less than I ms (Walton & Fozzard, 1979). Action potentials were recorded from cells on the surface of the preparations by use of conventional glass microelectrodes filled with 3M KCI, coupled to a high imput iitpedance d.c. amplifier with negative capacitance compensation (Neurolog).…”

Importance of physico‐chemical properties in determining the kinetics of the effects of Class I antiarrhythmic drugs on maximum rate of depolarization in guinea‐pig ventricle

“…The driving stimuli were provided from bipolar platinum electrodes producing square waves of 2 ms duration and sufficient intensity to produce a constant latency during a train of stimuli (Walton & Fozzard, 1979 Hondeghem & Cotner, 1978). The output of this instrument was simultaneously displayed on a storage oscilloscope and also recorded on FM tape from which it was later replayed at slow speed onto an X-Y plotter for analysis.…”

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

“…Since the Vms, is considered to be a valid index of conduction velocity (24,25), the former action suggests that at a physiological heart rate, (i) disopyramide causes a greater slowing of conduction in depolarized (ischemic) areas than in normopolarized ones, (ii) a change by this drug of a uni directional block into a bidirectional one is more possible in the heart with tachycardia than bradycardia, and (iii) disopyramide abolishes early extrasystoles more selectively in depolarized areas than normopolarized ones.…”