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Mechanisms underlying the tissue selectivity of the inhibitors of Ca2+ influx:
Verapamil requires the L-type Ca2+ channel to be open in order to gain access to its binding site.
The likelihood of an L-type Ca2+ channel being open is greater in cardiac muscle
(continuous action potential discharge) than in smooth muscle (more periodic action potential discharge).
More ready access to its binding site thus helps to explain the cardioselectivity of verapamil.
Verapamil may also exhibit greater binding affinity for the cardiac isoform of the
L-type Ca2+ channel compared with that found in smooth muscle.
The dihydropyridines may be selective for smooth muscle because smooth muscle has a lower resting membrane potential
than cardiac muscle and depolarisation increases the binding affinity of the dihydropyridines for the
L-type Ca2+ channel. The dihydropyridines may also exhibit greater binding affinity for the smooth muscle
isoform of the L-type Ca2+ channel compared with that found in cardiac muscle.
