Alkalinisation does not modify the effect of verapamil on myocardial Ca2+ current.

The effect of verapamil on L-type Ca2+ current (ICa) was compared at external pH 7.4 and 8.5 in rat ventricular myocytes. Alkalinisation increases the fraction of uncharged molecules of verapamil (pK 8.75) and thereby facilitates membrane permeation of the drug. Verapamil (1 microM) reduced the amplitude of ICa (ICa(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 ICa(peak) by 12 +/- 3%. It is suggested that the efficiency of verapamil is not influenced by the amount of protonation or membrane permeation.