Effects of the enantiomers of BayK 8644 on the charge movement of L-type Ca channels in guinea-pig ventricular myocytes

J Membr Biol. 2003 Jun 1;193(3):215-27. doi: 10.1007/s00232-003-2020-1.

Abstract

The effects of the agonist enantiomer S(-)Bay K 8644 on gating charge of L-type Ca channels were studied in single ventricular myocytes. From a holding potential (Vh) of -40 mV, saturating (250 nm) S(-)Bay K shifted the half-distribution voltage of the activation charge (Q1) vs. V curve -7.5 +/- 0.8 mV, almost identical to the shift produced in the Ba conductance vs. V curve (-7.7 +/- 2 mV). The maximum Q1 was reduced by 1.7 +/- 0.2 nC/microF, whereas Q2 (charge moved in inactivated channels) was increased in a similar amount (1.4 +/- 0.4 nC/microF). The steady-state availability curves for Q1, Q2, and Ba current showed almost identical negative shifts of -14.8 +/- 1.7 mV, -18.6 +/- 5.8 mV, and -15.2 +/- 2.7 mV, respectively. The effects of the antagonist enantiomer R(+)BayK 8644 were also studied, the Q1 vs. V curve was not significantly shifted, but Q1max (Vh = -40 mV) was reduced and the Q1 availability curve shifted by -24.6 +/- 1.2 mV. We concluded that: a) the left shift in the Q1 vs. V activation curve produced by S(-)BayK is a purely agonistic effect; b) S(-)BayK induced a significantly larger negative shift in the availability curve than in the Q1 vs. V relation, consistent with a direct promotion of inactivation; c) as expected for a more potent antagonist, R(+)Bay K induced a significantly larger negative shift in the availability curve than did S(-)Bay K.

Publication types

  • Comparative Study

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / chemistry*
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology*
  • Animals
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / physiology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart Ventricles / drug effects
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Isomerism
  • Membrane Potentials / drug effects*
  • Membrane Potentials / physiology*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology*
  • Static Electricity
  • Structure-Activity Relationship
  • Ventricular Function

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester