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(Circulation Research. 2005;97:35.)
© 2005 American Heart Association, Inc.

Cellular Biology

Ca²⁺ Sparks and Waves in Canine Purkinje Cells

A Triple Layered System of Ca²⁺ Activation

Bruno D. Stuyvers, Wen Dun, Scot Matkovich, Vincenzo Sorrentino, Penelope A. Boyden, Henk E.D.J. ter Keurs

From the Departments of Medicine (B.D.S., H.E.D.J.t.K.), Physiology, and Biophysics, University of Calgary, Alberta, Canada; the Departments of Pharmacology (W.D., P.A.B., H.E.D.J.t.K.) and Molecular Cardiology (S.M.), Center for Molecular Therapeutics, Columbia University, New York; and the Department of Neuroscience (V.S.), University of Siena, Italy.

Correspondence to Bruno D. Stuyvers, Cardiovascular Research Group, Department of Medicine, Physiology and Biophysics, University of Calgary, Health Science Center/R1665, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1 Canada. E-mail stuyvers{at}ucalgary.ca

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-µm 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 µm 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.

Key Words: Purkinje • Ca²⁺ sparks • Ca²⁺ waves • Ca transients • automaticity

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