Voltage and calcium-gated potassium channels: Functional expression and therapeutic potential in the vasculature

The dual expression of voltage-gated K+ (K-V) channels and high conductance Ca2+-activated K+ (BKCa) channels in vascular smooth muscle membranes prov ides a fundamental mechanism for regulating the membrane potential and tone of resistance arteries. The distribution of these channels appears to diff er between vascular regions, and diverse channel phenotypes resulting from molecular heterogeneity may mediate distinct patterns of excitability and c ontraction in specific vascular beds. Under physiological conditions, K-V a nd BKCa channels appear to act in concert to regulate the level of contract ion in the cerebral, coronary and pulmonary circulations, and thereby maint ain blood flow to vital tissues. However, during cardiovascular pathologies , this profile of K+ channel function may be disrupted in vascular smooth m uscle membranes, and unique disease-specific patterns of K-V and BKCa chann el expression may emerge. Under these conditions, drug therapies designed t o normalize K+ channel expression or target overexpressed channels in arter ial smooth muscle membranes may have potential value for the treatment of v ascular diseases.