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

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 m M ) using the patch‐clamp technique. The influx of Ca 2+ had characteristics of L‐type I Ca ( I Ca(L) ). 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 μ M ) and DTBHA (30 μ M ) decreased I Ca(L) by 48.9% and 45.2%, respectively. This inhibition was only partially reversible. In contrast, DIBHA (up to 50 μ M ) was devoided of effects on I Ca(L) . 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. 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. 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.British Journal of Pharmacology (2001) 132 , 1326–1332; doi: 10.1038/sj.bjp.0703935