title: Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+ release induced by voltage-gated Ca2+ entry.
abstract: Membrane depolarization triggers Ca(2+) release from the sarcoplasmic reticulum (SR) in skeletal muscles via direct interaction between the voltage-gated L-type Ca(2+) channels (the dihydropyridine receptors; VGCCs) and ryanodine receptors (RyRs), while in cardiac muscles Ca(2+) entry through VGCCs triggers RyR-mediated Ca(2+) release via a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Here we demonstrate that in phasic smooth muscle of the guinea-pig small intestine, excitation evoked by muscarinic receptor activation triggers an abrupt Ca(2+) release from sub-plasmalemmal (sub-PM) SR elements enriched with inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and poor in RyRs. This was followed by a lesser rise, or oscillations in [Ca(2+)](i). The initial abrupt sub-PM [Ca(2+)](i) upstroke was all but abolished by block of VGCCs (by 5 microM nicardipine), depletion of intracellular Ca(2+) stores (with 10 microM cyclopiazonic acid) or inhibition of IP(3)Rs (by 2 microM xestospongin C or 30 microM 2-APB), but was not affected by block of RyRs (by 50-100 microM tetracaine or 100 microM ryanodine). Inhibition of either IP(3)Rs or RyRs attenuated phasic muscarinic contraction by 73%. Thus, in contrast to cardiac muscles, excitation-contraction coupling in this phasic visceral smooth muscle occurs by Ca(2+) entry through VGCCs which evokes an initial IP(3)R-mediated Ca(2+) release activated via a CICR mechanism.
authors.affiliation: Division of Basic Medical Sciences, Ion Channels and Cell Signalling Centre, St. George's University of London, UK. gordienk@sgul.ac.uk
authors.forename: D V
authors.initials: DV
authors.lastname: Gordienko
authors.forename: M I
authors.initials: MI
authors.lastname: Harhun
authors.forename: M V
authors.initials: MV
authors.lastname: Kustov
authors.forename: V
authors.initials: V
authors.lastname: Pucovský
authors.forename: T B
authors.initials: TB
authors.lastname: Bolton
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D011976:Receptors, Muscarinic; D019837:Ryanodine Receptor Calcium Release Channel; C511704:xestospongin C; D013748:Tetracaine; D002217:Carbachol; D009529:Nicardipine; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium