title: Two Ca2+ entry pathways mediate InsP3-sensitive store refilling in guinea-pig colonic smooth muscle.
abstract: Sarcolemma Ca2+ influx, necessary for store refilling, was well maintained, over a wide range (-70 to + 40 mV) of membrane voltages, in guinea-pig single circular colonic smooth muscle cells, as indicated by the magnitude of InsP3-evoked Ca2+ transients. This apparent voltage independence of store refilling was achieved by the activity of sarcolemma Ca2+ channels some of which were voltage gated while others were not. At negative membrane potentials (e.g. -70 mV), Ca2+ influx through channels which lacked voltage gating provided for store refilling while at positive membrane potentials (e.g. +40 mV) voltage-gated Ca2+ channels were largely responsible. Sarcolemma voltage-gated Ca2+ currents were not activated following store depletion. Removal of external Ca2+ or the addition of the Ca2+ channel blocker nimodipine (1 microM) inhibited store refilling, as assessed by the magnitude of InsP3-evoked Ca2+ transients, with little or no change in bulk average cytoplasmic Ca2+ concentration. One hypothesis for these results is that the store may refill from a high subsarcolemma Ca2+ gradient. Influx via channels, some of which are voltage gated and others which lack voltage gating, may permit the establishment of a subsarcolemma Ca2+ gradient. Store access to the gradient allows InsP3-evoked Ca2+ signalling to be maintained over a wide voltage range in colonic smooth muscle.
authors.affiliation: Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK. j.mccarron@bio.gla.ac.uk
authors.forename: J G
authors.initials: JG
authors.lastname: McCarron
authors.forename: E R
authors.initials: ER
authors.lastname: Flynn
authors.forename: K N
authors.initials: KN
authors.lastname: Bradley
authors.forename: T C
authors.initials: TC
authors.lastname: Muir
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism*; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014966:Xanthenes; C059715:Fluo-3; D004533:Egtazic Acid; D009553:Nimodipine; D015544:Inositol 1,4,5-Trisphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium