Endothelin-induced electrical activity and calcium dynamics in vascular smooth muscle cells: a model study.
A model is proposed to describe the electrical activity and intracellular calcium dynamics of vascular smooth muscle cells (SMC) induced by endothelin (ET1). The conductance of the nonselective channels (NSCs), proportional to the ET1-receptor complex (ET . R), is intracellular calcium dependent. Inositol (1,4,5)-trisphosphate (IP3) produced by ET1 releases Ca2+ from the IP3-sensitive Ca2+ store. The transient increase of intracellular Ca2+ triggers the release of Ca2+ from the Ca(2+)-sensitive store by a Ca(2+)-induced Ca2+ (CICR) mechanism and activates the Ca(2+)-activated K+ current (IK,Ca). The inward current (Iin) via the NSC can depolarize the cell to a level at which the L-type Ca2+ current becomes activated (ICa). The level of depolarization is determined by the relative amplitude of (Iin + ICa + IK,Ca) and the voltage- and time-dependent K+ current. The model simulations show that (a) in cells without a CICR mechanism, short-lasting stimulation by ET1 elicits higher membrane potential and Ca2+ than long-lasting stimulation; (b) in cells with or without a CICR mechanism, a reduction of normal membrane capacitance (1 muf/cm2) results in either significant and sustaining or oscillatory membrane potential and intracellular calcium concentration. The applicability of the model to the study of electrical activity and calcium dynamics associated with hypercholesterolemia is discussed.
Wong
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AY
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Klassen
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GA
D000818:Animals; D001158:Arteries / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D017466:Receptors, Endothelin / Q000502:physiology; D014680:Veins / Q000502:physiology
D019332:Endothelin-1; D015221:Potassium Channels; D017466:Receptors, Endothelin; D002118:Calcium