Effects of some sterically hindered phenols on whole-cell Ca(2+) current of guinea-pig gastric fundus smooth muscle cells

Br J Pharmacol. 2001 Mar;132(6):1326-32. doi: 10.1038/sj.bjp.0703935.

Abstract

1. The aim of the present study was to investigate the effects of extracellular application of some sterically-hindered phenols, namely 3-t-butyl-4-hydroxyanisole (BHA), 3,5-di-t-butyl-4-hydroxyanisole (DTBHA) and the dimer of BHA, 2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxydiphenyl (DIBHA), on the whole-cell Ca(2+) current (I(Ca)) of freshly isolated smooth muscle cells from the guinea-pig gastric fundus, in the presence of a range of Ca(2+) concentrations (1 -- 5 mM) using the patch-clamp technique. The influx of Ca(2+) had characteristics of L-type I(Ca) (I(Ca(L))). 2. BHA as well as DTBHA inhibited I(Ca(L)) in a concentration-dependent manner, during depolarization to 10 mV from a holding potential of -50 mV. Bath application of BHA (50 microM) and DTBHA (30 microM) decreased I(Ca(L)) by 48.9% and 45.2%, respectively. This inhibition was only partially reversible. In contrast, DIBHA (up to 50 microM) was devoided of effects on I(Ca(L)). 3. BHA inhibition of I(Ca(L)) was voltage-dependent and inversely related to the external concentration of Ca(2+). On the other hand, DTBHA inhibition was only voltage-dependent. 4. BHA and DTBHA shifted the voltage range of the steady-state inactivation curve to more negative potentials by 8 mV at the mid-potential of the curve, without affecting the activation curve. Furthermore, BHA and DTBHA did not modify the time-course of the current decay. 5. We conclude that the inhibition of I(Ca(L)) by BHA and DTBHA is qualitatively similar to that of a Ca(2+) channel blocker and is characterized by the stabilizing effect of the inactivated state of the channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Butylated Hydroxyanisole / analogs & derivatives
  • Butylated Hydroxyanisole / pharmacology*
  • Calcium / metabolism*
  • Electrophysiology
  • Gastric Fundus / cytology
  • Gastric Fundus / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Patch-Clamp Techniques

Substances

  • Antioxidants
  • Butylated Hydroxyanisole
  • 3,5-di-tert-butyl-4-hydroxyanisole
  • 2,2'-dihydroxy-3,3'-di-tert-butyl-5,5'-dimethoxydiphenyl
  • Calcium