Regulation of 4 aminopyridine-sensitive, delayed rectifier K+ channels in vascular smooth muscle by phosphorylation

Voltage-gated delayed rectifier K+ current (K-V) that is sensitive to 4-aminopyridine (4AP) block has been identified in all vascular smooth muscle tissues studied to date. These channels conduct outward, hyperpolarizing K+ current that influences resting membrane potential and contributes to repolarization of action potentials. Smooth muscle cells in most arterial resistance vessels regulate Ca2+ influx and contractile tone by low amplitude, tonic changes in membrane potential. Block of K-V with 4-aminopyridine leads to contraction and an enhanced myogenic response to increased intravascular pressure. We investigated the. modulation of K-V currents in isolated, freshly dispersed smooth muscle cells from rabbit portal vein and coronary arteries in whole-cell voltage clamp experiments. Our findings indicate that K-V channels are regulated by signal transduction mechanisms involving vasoactive agonists that activate cAMP-dependent protein kinase (PKA) or protein kinase C (PKC). In this paper, the properties and potential function of K-V channels in vascular smooth muscle are reviewed. Further, the regulation and potential role of alterations in K-V due to beta-adrenoceptor agonists, adenylyl cyclase and PKA, as well as angiotensin II, diacylglycerol, and PKC are discussed.