Intracellular N-methyl-d-glucamine modifies the kinetics and voltage-dependence of the calcium current in guinea pig ventricular heart cells

Abstract

The effects of internal substitution of the impermeant cation N-methyl-D-glucamine (NMG) for Cs ion on the properties of the Ca-current (L-type channel) were examined in single guinea pig cardiac myocytes with the whole-cell clamp technique. The properties of the cobalt-sensitive Ca current recorded in the presence of internal NMG or Cs were compared and the results were as follows. (1) The overall duration of the Ca-dependent slow action potential was markedly increased in the presence of internal NMG (6-fold at 0 mV) when compared to action potentials recorded with internal Cs. (2) The cobalt-sensitive Ca currents recorded with internal NMG or Cs had similar reversal potentials. However, in the presence of internal NMG, the maximum current density of the cobalt-sensitive Ca current was decreased and both the threshold and potential at which maximum current occurred were negatively shifted. (3) Voltage-dependence of steady-state activation, but not inactivation, of the cobalt-sensitive Ca current was shifted by -11.8 mV with internal NMG. (4) NMG increased the half-time of activation and inactivation of the cobalt-sensitive Ca current. The voltage-dependence of the half-time of inactivation was shifted by about -30 mV between 0 and +60 mV. Time constants measurements showed that NMG affected more the slow phase of inactivation of the Ca current. (5) When Ba was the charge carrier, NMG removed most of the inactivation of the current, suggesting a slowing of the voltage-dependent process of inactivation. (6) The results are consistent with a modification of the properties of the Ca channel by internal NMG.