Inactivation, reactivation and pacing dependence of calcium current in frog cardiocytes: correlation with current density.

Abstract

SUMMARY1. Ca2+ currents were measured in single cells isolated from frog ventricle using the whole-cell patch clamp technique and a perfused pipette. K+ currents were blocked with intracellular (120 mM) and extracellular (20 mM) Cs+.2. A single type of Ca2+ current (ICa) was found in these cells. The current activated at voltages positive to -30 mV, exhibited a symmetrical current-voltage relationship with a peak at 0 mV, and was slowly inactivating with Ba2+ as charge carrier.3. Large variations in ICa amplitude were observed from cell to cell (ICa at 0 mV = 29341 + 283-3 pA; N = 152). These variations were not due simply to differences in cell membrane area, which was estimated by cell membrane capacitance (Cm), because the density of Ca2+ current (dIca = Ica/Cm) also varied significantly from cell to cell (1I3-28 pA/pF at 0 mV; mean+ S.D. = 4-49+3-96; N = 152).4. The inactivation curve of ICa was a complex function of mnembrane potential. 200 ms pre-pulses to voltages between -60 and + 20 mV progressively inactivated ICa elicited by a subsequent test pulse with half-maximal inactivation occurring for pre-pulses to -40 mV. With pre-pulses positive to + 20 mV, ICa elicited by the test pulse became progressively larger. The degree of inactivation induced by a 200 ms depolarization to potentials more positive than + 20 mV varied significantly from cell to cell, while no such variations were observed in the negative range of membrane potentials.5. The time course of reactivation (i.e. removal from inactivation) of ICa at -80 mV often exhibited an overshoot. The amplitude of the overshoot varied between 100% (i.e. no overshoot) and z 180% in eighty-one cells.6. The degree of inactivation at positive potentials (+ 100 mV) and the amplitude * Present address:

Alteration of the L‐type calcium current in guinea‐pig single ventricular myocytes by heptaminol hydrochloride

“…As described by others (Argibay et al, 1988;Tseng, 1988; but see also Schouten & Morad, 1989) and shown in Figure 4, ICa recovery kinetics depended on the membrane holding potential. They were more rapid as the HP was more negative (half a -60 Voltage ( Prepulse potential (mV) (Figure 4a).…”

“…This increase in [Ca2+]i may result from: (1) a release of membrane bound Ca2" (Vassort et al, 1986); (2) an inhibition of Na'-Ca2" exchange mechanism (Michaelis & Michaelis, 1983;Philipson, 1984;Haworth et al, 1989) and of sarcolemmal and intracellular membrane Ca-ATPases (Salama & Scarpa, 1983;Ohnishi et al, 1984). In order to explain their effects on ICa characteristics, Mongo & Vassort (1990) have proposed the participation of an increase in [Ca2+]i as a mechanism of action of n-alkanols and halogenated compounds in addition to those previously described (see Introduction and also Meszaros & Pappano, 1990 (Mentrard et al, 1984;Argibay et al, 1988;Tseng, 1988) (Mentrard et al, 1984). This reduction, although significant (P <0.02, n = 8), appeared to be not very pronounced; this may be due to the use of EGTA (10 mM) in the patch pipette to buffer intracellular Ca2+ to avoid cell contraction.…”

An endogenous ‘hypertensive factor’ enhances the voltage‐dependent calcium current

“…These effects of HF are similar to those seen in the presence of dihydropyridine calcium channel agonists [9-121 and less similar to those seen following phosphorylation of the calcium channel [5,7,13]. Inactivation of Ica is thought to consist of both voltage-and calcium-dependent components [ 141.…”

“…This 400 ms prepulse was sufficiently long to ensure that the calcium current was in steady-state inactivation. The inactivation curve exhibited a characteristic U-shape (fig3A) [7]. In the presence of HF, the inactivation of Ica was greater at more negative potentials.…”

“…HF shifted El/z from -25.2 to -37.8 and increased the slope factor from 5.6 to 6.4. The reactivation, or time course of the recovery from steady-state inactivation, of the calcium current, was measured at 0 mV [7]. HF did not affect reactivation of Ica (n = 3).…”