Apamin, a highly potent blocker of the TTX- and Mn2(+)-insensitive fast transient Na+ current in young embryonic heart

J Mol Cell Cardiol. 1991 Jan;23(1):25-39. doi: 10.1016/0022-2828(91)90036-l.

Abstract

The whole-cell current clamp and voltage clamp techniques were used to record the slow Na+ action potentials (APs) and the inward current in cultured single ventricular cells isolated from young (3 day-old) embryonic chicks. The slow Na+ APs had a +Vmax of 21.5 +/- 7.5 V/s (in 10 different single cells) and the macroscopic inward current responsible for the rising phase of these APs was a fast transient (ft) current. The ft inward current was sensitive to changes in [Na]o but not to changes in [Ca]o. This channel was found to be permeable to Li+ and Ba2+. Analysis of Na+ current decay suggests a second-order process of current decay. The slow Na+ APs and the ft inward current were insensitive to tetrodotoxin (TTX) and Mn2+. This current was also insensitive to the inorganic Ca2+ blockers, Ni2+, Cd2+ and La3+. At low concentration (10(-9)-10(-6) M) the organic Ca2+ blockers, (-)D888 and nifedipine had no effect on the TTX- and Mn2(+)-insensitive INa. However, at a high concentration (10(-5) M), the Ca2+ blockers, (-)D888 and nifedipine, completely blocked the slow Na+ APs and the TTX- and Mn2(+)-insensitive ft inward Na+ current responsible for the rising phase of the APs. High concentration of verapamil (10(-5) M) and D-600 (10(-5) M) had little depressant effects due to their frequency dependence. Apamin, a toxin in the bee venom, that was previously reported by our group to block the slow Ca2+ APs (Bkaily et al., 1985) and the slow Ca2+ current (Bkaily et al., 1988b), greatly decreased the TTX- and Mn2(+)-insensitive ft INa at 10(-10) M. Thus, the inward current responsible for the rising phase of the slow Na+ APs in 3 day-old embryonic chick heart shows fast transient activation and is TTX- and Mn2(+)-insensitive. This channel is highly sensitive to apamin and shares few characteristics with the Ca2+ channel and the TTX-sensitive fast Na+ channel.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Apamin / pharmacology*
  • Barium / pharmacokinetics
  • Barium / pharmacology
  • Calcium / pharmacokinetics
  • Calcium / pharmacology
  • Cell Membrane Permeability / drug effects
  • Chick Embryo
  • Electric Conductivity / drug effects
  • Heart / drug effects
  • Heart / embryology
  • Lithium / pharmacokinetics
  • Lithium / pharmacology
  • Manganese / pharmacology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Nifedipine / pharmacology
  • Sodium / metabolism*
  • Sodium / pharmacokinetics
  • Tetrodotoxin / pharmacology*
  • Verapamil / analogs & derivatives
  • Verapamil / pharmacology

Substances

  • Apamin
  • Barium
  • Manganese
  • Tetrodotoxin
  • 4-desmethoxyverapamil
  • Lithium
  • Sodium
  • Verapamil
  • Nifedipine
  • Calcium