Ca2+ influx via the L-type Ca2+ channel during tail current and above current reversal potential in ferret ventricular myocytes

J Physiol. 2000 Feb 15;523 Pt 1(Pt 1):57-66. doi: 10.1111/j.1469-7793.2000.t01-2-00057.x.

Abstract

1. Current through L-type Ca2+ channels (ICa) was measured electrophysiologically at the same time as Ca2+ influx was measured by trapping entering Ca2+ with a high concentration of indo-1 (> 1 mM) in ferret ventricular myocytes. 2. Na+-free conditions prevented Na+-Ca2+ exchange and K+ currents were blocked by Cs+ and TEA. Thapsigargin (5 microM) prevented Ca2+ uptake and release by the sarcoplasmic reticulum. ICa was pre-activated by brief pulses to +120 mV (the equilibrium potential for Ca2+, ECa), followed by steps to different membrane potentials (Em, -80 to +100 mV), in some cases in the presence of the Ca2+ channel agonist FPL-64176. 3. Integrated ICa ( 82 ICa) was linearly related to the change in the concentration of Ca2+ bound to indo-1, which was assessed by the fluorescence difference signal DeltaFd (Fd = F500 - F400). This created an internal calibration of DeltaFd as a measure of Ca2+ influx. 4. The DeltaFd/ 82 ICadt relationship was virtually unchanged at all measurable inward ICa (at Em from -80 to +50 mV). This indicates that the fractional current carried by Ca2+ and channel selectivity are unchanged over this Em range, and also that the selectivity for Ca2+ is very high. 5. Ca2+ influx was readily detected by DeltaFd beyond the ICa reversal potential (+65 to +100 mV) and was not abolished until Em was +120 mV (i.e. ECa). This is explained by the fact that inward Ca2+ flux at the ICa reversal potential is exactly balanced by outward Cs+ current through the Ca2+ channels and can be described by classic Goldman flux analysis with a Ca2+/Cs+ selectivity of the order of 5000. 6. This result also emphasizes that net Ca2+ influx via Ca2+ channels occurs over a voltage range where the net channel current is outward.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, L-Type / physiology*
  • Electric Conductivity
  • Electrophysiology
  • Heart Ventricles
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Pyrroles / pharmacology

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Pyrroles
  • FPL 64176
  • Calcium