On the relationship between $$\dot V_{\max }$$ of slow responses and Ca-current availability in whole-cell clamped guinea pig heart cells

Abstract

The relationship between Ca current availability and maximum rate of rise (V max) of slow responses was determined in the same single guinea pig ventricular heart cell under voltage and current clamp conditions (whole-cell clamp technique). The results are as follows. (1) Cell capacitance measured in 32 cells from the current response to a fast ramp voltage-clamp pulse (119.6 +/- 4.6 pF, mean +/- SE) or from Vmax values at a holding potential of -50 or -40 mV (118.6 +/- 5.3 pF) are identical. (2) In control conditions ([Ca]o 1.8, [K]o 4 and [Cs]i 140 mM), voltage-dependence of steady-state inactivation of Ca current (ICa) or Vmax are similar up to -35 mV. However, Vmax significantly (P less than 0.005) underestimates ICa availability at more positive potentials. At -30 mV, ICa and Vmax amplitudes represent respectively 35.6 and 22.4% (n = 14) of their maximum value. (3) In the presence of 50 nM isoprenaline, Vmax and the underlying ICa are respectively increased by 79.2 +/- 13.8% and 71.2 +/- 13.8% (n = 15). No statistically significant deviation from linearity is then observed. (4) When Vmax amplitude is expressed as a function of ICa density, an almost linear relationship is observed for Vmax values between 0 and 25 V/s. Vmax is then best described by the equation: Vmax (V/s) = 1.043 ICa (pA/pF) -0.514 (46 cells). (5) We conclude that, under conditions that minimize outward currents, Vmax of slow responses accurately measures ICa amplitude, except when ICa is decreased to less than 40% of its maximum control amplitude (i.e., below 4 pA/pF). At that point, Vmax underestimates ICa.