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

Area of Science:

• Cardiovascular Pharmacology
• Ion Channel Physiology

Background:

• Verapamil is a calcium channel blocker used to treat cardiovascular conditions.
• The drug's efficacy may be influenced by pH due to its pKa of 8.75.
• Extracellular alkalinization can affect ion channel function.

Purpose of the Study:

• To investigate the effect of extracellular pH on verapamil's inhibition of L-type calcium current (ICa) in rat ventricular myocytes.
• To determine if changes in verapamil's charge state at different pH levels impact its efficacy.

Main Methods:

• Patch-clamp electrophysiology was used to measure L-type Ca2+ current (ICa) in isolated rat ventricular myocytes.
• Verapamil (1 microM) was applied at two extracellular pH levels: 7.4 and 8.5.
• The effect of alkalinization alone on ICa was also assessed.

Main Results:

• Verapamil reduced ICa amplitude by 36% at pH 7.4 and 40% at pH 8.5.
• Extracellular alkalinization (pH 7.4 to 8.5) alone increased ICa amplitude by 12%.
• The percentage reduction in ICa by verapamil was similar at both pH values.

Conclusions:

• The study suggests that verapamil's efficiency in blocking L-type Ca2+ channels is not significantly affected by extracellular pH.
• Neither the degree of verapamil protonation nor its membrane permeation appears to be the primary determinant of its efficacy in this context.
• These findings contribute to understanding the pharmacodynamics of verapamil in varying physiological conditions.