title: Ca2+ sparks and waves in canine purkinje cells: a triple layered system of Ca2+ activation.
abstract: We have investigated the subcellular spontaneous Ca2+ events in canine Purkinje cells using laser scanning confocal microscopy. Three types of Ca2+ transient were found: (1) nonpropagating Ca2+ transients that originate directly under the sarcolemma and lead to (2) small Ca2+ wavelets in a region limited to 6-microm depth under the sarcolemma causing (3) large Ca2+ waves that travel throughout the cell (CWWs). Immunocytochemical studies revealed 3 layers of Ca2+ channels: (1) channels associated with type 1 IP3 receptors (IP3R1) and type 3 ryanodine receptors (RyR3) are prominent directly under the sarcolemma; (2) type 2 ryanodine receptors (RyR2s) are present throughout the cell but virtually absent in a layer between 2 and 4 microm below the sarcolemma (Sub-SL); (3) type 3 ryanodine receptors (RyR3) is the dominant Ca2+ release channel in the Sub-SL. Simulations of both nonpropagating and propagating transients show that the generators of Ca2+ wavelets differ from those of the CWWs with the threshold of the former being less than that of the latter. Thus, Purkinje cells contain a functional and structural Ca2+ system responsible for the mechanism that translates Ca2+ release occurring directly under the sarcolemma into rapid Ca2+ release in the Sub-SL, which then initiates large-amplitude long lasting Ca2+ releases underlying CWWs. The sequence of spontaneous diastolic Ca2+ transients that starts directly under the sarcolemma and leads to Ca2+ wavelets and CWWs is important because CWWs have been shown to cause nondriven electrical activity.
authors.affiliation: Cardiovascular Research Group, Department of Medicine, Physiology and Biophysics, University of Calgary, Health Science Center/R1665, Calgary, Alberta, Canada. stuyvers@ucalgary.ca
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Stuyvers
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: Scot
authors.initials: S
authors.lastname: Matkovich
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sorrentino
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Henk E D J
authors.initials: HE
authors.lastname: ter Keurs
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis; D004058:Diffusion; D004285:Dogs; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011689:Purkinje Cells / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium