title: The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction.
abstract: We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (approximately 2 microm) intervals throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a fully regenerative manner through the interior of a cell. Rather, there was a diminishing centripetal propagation of calcium. The lack of regeneration was due to mitochondria and SERCA pumps preventing the inward movement of calcium. Inhibiting these calcium buffering mechanisms allowed the globalisation of action potential-evoked responses. In addition, physiological positive inotropic agents, such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led to regenerative global responses. The consequence of globalising calcium signals was a significant increase in cellular contraction. These data indicate how calcium signals and their consequences are determined by the interplay of multiple subcellular calcium management systems.
authors.affiliation: Laboratory of Molecular Signalling, The Babraham Institute, Babraham Hall, Babraham, Cambridge, CB2 4AT, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mackenzie
authors.forename: H Llewelyn
authors.initials: HL
authors.lastname: Roderick
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Berridge
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Martin D
authors.initials: MD
authors.lastname: Bootman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006325:Heart Atria / Q000166:cytology*; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002118:Calcium