Ca2+ channels, ryanodine receptors and Ca2+-activated K+ channels: a functional unit for regulating arterial tone

Local calcium transients ('Ca2+ sparks') are thought to be elementary Ca2signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clust ered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). in arterial smooth muscle, Ca2+ sparks appear to be involved in opposing th e tonic contraction of the blood vessel. Intravascular pressure causes a gr aded membrane potential depolarization to approximately -40 mV, an elevatio n of arterial wall [Ca2+](i) and contraction ('myogenic tone') of arteries. Ca2+ sparks activate calcium-sensitive K+ (K-Ca) channels in the sarcolemm al membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or o f K-Ca channels by iberiotoxin, leads to membrane depolarization, activatio n of L-type voltage-gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of K- Ca channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The mo dulation of Ca2+ spark frequency and amplitude by membrane potential, cycli c nucleotides and protein kinase C will be explored. The role of local Ca2 entry through voltage-dependent Ca2+ channels in the regulation of Ca2+ sp ark properties will also be examined. Finally, using functional evidence fr om cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and K-Ca channels function as a coupled unit, through Ca2+ and voltage, to regulate arterial smooth musc le membrane potential and vascular tone.