Abstract
The effect of verapamil on L-type Ca 2+ current ( I Ca) was compared at external pH 7.4 and 8.5 in rat ventricular myocytes. Alkalinisation increases the fraction of uncharged molecules of verapamil (p K 8.75) and thereby facilitates membrane permeation of the drug. Verapamil (1 μM) reduced the amplitude of I Ca ( I Ca(peak)) by 36 ± 4% at pH 7.4 and by 40 ± 6% at pH 8.5, whereas alkalinisation from pH 7.4 to 8.5, without drug, increased I Ca(peak) by 12 ± 3%. It is suggested that the efficiency of verapamil is not influenced by the amount of protonation or membrane permeation.
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