Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels.
Intracellular calcium ions are involved in the regulation of nearly every aspect of cell function. In smooth muscle, Ca2+ can be delivered to Ca2+-sensitive effector molecules either by influx through plasma membrane ion channels or by intracellular Ca2+ release events. Ca2+ sparks are transient local increases in intracellular Ca2+ that arise from the opening of ryanodine-sensitive Ca2+ release channels (ryanodine receptors) located in the sarcoplasmic reticulum. In arterial myocytes, Ca2+ sparks occur near the plasma membrane and act to deliver high (microM) local Ca2+ to plasmalemmal Ca2+-sensitive ion channels, without directly altering global cytosolic Ca2+ concentrations. The two major ion channel targets of Ca2+ sparks are Ca2+-activated chloride (Cl(Ca)) channels and large-conductance Ca2+-activated potassium (BK) channels. The activation of BK channels by Ca2+ sparks play an important role in the regulation of arterial diameter and appear to be involved in the action of a variety of vasodilators. The coupling of Ca2+ sparks to BK channels can be influenced by a number of factors including membrane potential and modulatory beta subunits of BK channels. Cl(Ca) channels, while not present in all smooth muscle, can also be activated by Ca2+ sparks in some types of smooth muscle. Ca2+ sparks can also influence the activity of Ca2+-dependent transcription factors and expression of immediate early response genes such as c-fos. In summary, Ca2+ sparks are local Ca2+ signaling events that in smooth muscle can act on plasma membrane ion channels to influence excitation-contraction coupling as well as gene expression.
Wellman
George C
GC
Department of Pharmacology, The University of Vermont College of Medicine, Given Building, Room B-321, 89 Beaumont Avenue, Burlington, VT 05405, USA. gwellman@zoo.uvm.edu
Nelson
Mark T
MT
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D018118:Chloride Channels; D007473:Ion Channels; D024681:Potassium Channels, Calcium-Activated; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium