title: Ca2+ channels, 'quantized' Ca2+ release, and differentiation of myocytes in the cardiovascular system.
abstract: The application of confocal microscopy to cardiac and skeletal muscle has resulted in the observation of transient, spatially localized elevations in [Ca2+]i, termed 'Ca2+ sparks'. Ca2+ sparks are thought to represent 'elementary' Ca2+ release events, which arise from one or more ryanodine receptor (RyR) channels in the sarcoplasmic reticulum. In cardiac muscle, Ca2+ sparks appear to be key elements of excitation-contraction coupling, in which the global [Ca2+]i transient is thought to involve the recruitment of Ca2+ sparks, each of which is controlled locally by single coassociated L-type Ca2+ channels. Recently, Ca2+ sparks have been detected in smooth muscle cells of arteries. In this review, we analyse the complex relationship of Ca2+ influx and Ca2+ release with local, subcellular Ca2+ microdomains in light of recent studies on Ca2+ sparks in cardiovascular cells. We performed a comparative analysis of 'elementary' Ca2+ release units in mouse, rat and human arterial smooth muscle cells, using measurements of Ca2+ sparks and plasmalemmal K(Ca) currents activated by Ca2+ sparks (STOCs). Furthermore, the appearance of Ca2+ sparks during ontogeny of arterial smooth muscle is explored. Using intact pressurized arteries, we have investigated whether RyRs causing Ca2+ sparks (but not smaller 'quantized' Ca2+ release events, e.g. hypothetical 'Ca2+ quarks') function as key signals that, through membrane potential and global cytoplasmic [Ca2+], oppose arterial myogenic tone and influence vasorelaxation. We believe that voltage-dependent Ca2+ channels and local RyR-related Ca2+ signals are important in differentiation, proliferation, and gene expression. Our findings suggest that 'elementary' Ca2+ release units may represent novel potent therapeutic targets for regulating function of intact arterial smooth muscle tissue.
authors.affiliation: Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, Charité University Hospitals, Humboldt University Berlin, Germany. gollasch@fvk-berlin.de
authors.forename: M
authors.initials: M
authors.lastname: Gollasch
authors.forename: M
authors.initials: M
authors.lastname: Löhn
authors.forename: M
authors.initials: M
authors.lastname: Furstenau
authors.forename: M T
authors.initials: MT
authors.lastname: Nelson
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: H
authors.initials: H
authors.lastname: Haller
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002319:Cardiovascular System / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D051381:Rats
chemical_list: D015220:Calcium Channels; D002118:Calcium