Regulation of 4-aminopyridine-sensitive, delayed rectifier K+ channels in vascular smooth muscle by phosphorylation.
Voltage-gated, delayed rectifier K+ current (KV) 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 KV with 4-aminopyridine leads to contraction and an enhanced myogenic response to increased intravascular pressure. We investigated the modulation of KV 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 KV 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 KV channels in vascular smooth muscle are reviewed. Further, the regulation and potential role of alterations in KV due to beta-adrenoceptor agonists, adenylyl cyclase and PKA, as well as angiotensin II, diacylglycerol, and PKC are discussed.
Cole
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WC
Smooth Muscle Research Group, University of Calgary, AB, Canada.
Clément-Chomienne
O
O
Aiello
E A
EA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D015640:Ion Channel Gating; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
D015220:Calcium Channels; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015761:4-Aminopyridine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C