Ca2+ channels, ryanodine receptors and Ca(2+)-activated K+ channels: a functional unit for regulating arterial tone.

J Jaggar, G Wellman, T Heppner, V Porter, G Perez, M Gollasch, T Kleppisch, M Rubart, A Stevenson, W Lederer, H Knot, A Bonev, MT Nelson

    Research output: Contribution to journalArticlepeer-review


    Local calcium transients ('Ca2+ sparks') are thought to be elementary Ca2+ signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clustered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In arterial smooth muscle, Ca2+ sparks appear to be involved in opposing the tonic contraction of the blood vessel. Intravascular pressure causes a graded membrane potential depolarization to approximately -40 mV, an elevation of arterial wall [Ca2+]i and contraction ('myogenic tone') of arteries. Ca2+ sparks activate calcium-sensitive K+ (KCa) channels in the sarcolemmal membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or of KCa channels by iberiotoxin, leads to membrane depolarization, activation of L-type voltage-gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of KCa channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The modulation of Ca2+ spark frequency and amplitude by membrane potential, cyclic nucleotides and protein kinase C will be explored. The role of local Ca2+ entry through voltage-dependent Ca2+ channels in the regulation of Ca2+ spark properties will also be examined. Finally, using functional evidence from cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and KCa channels function as a coupled unit, through Ca2+ and voltage, to regulate arterial smooth muscle membrane potential and vascular tone.
    Original languageEnglish
    JournalActa Physiologica Scandinavica
    Volume164( 4)
    Publication statusPublished - Dec 1998


    • Animals
    • cytology: Arteries
    • physiology: Calcium
    • physiology: Calcium Channels
    • physiology: Calcium Signaling
    • Humans
    • physiology: Muscle Tonus
    • cytology: Muscle, Smooth, Vascular
    • physiology: Potassium Channels
    • physiology: Ryanodine Receptor Calcium Release Channel
    • physiology: Up-Regulation


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