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(Circulation Research. 2007;100:1605.)
© 2007 American Heart Association, Inc.

Cellular Biology

Store-Operated Ca²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

Yue-Kun Ju, Yi Chu, Herve Chaulet, Donna Lai, Othon L. Gervasio, Robert M. Graham, Mark B. Cannell, David G. Allen

From the School of Medical Sciences and Bosch Institute (Y.-K.J., Y.C., D.L., O.L.G., D.G.A.), University of Sydney, and Victor Chang Cardiac Research Institute (H.C., R.M.G.), Australia; and the The Faculty of Medical and Health Sciences (M.B.C.), University of Auckland, New Zealand.

Correspondence to Yue-kun Ju, School of Medical Sciences (F13), University of Sydney, Sydney, NSW 2006, Australia. E-mail ju{at}physiol.usyd.edu.au

Store-operated Ca²⁺ entry was investigated in isolated mouse sinoatrial nodes (SAN) dissected from right atria and loaded with Ca²⁺ indicators. Incubation of the SAN in Ca²⁺-free solution caused a substantial decrease in resting intracellular Ca²⁺ concentration ([Ca²⁺]_i) and stopped pacemaker activity. Reintroduction of Ca²⁺ in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca²⁺ pump inhibitor, led to sustained elevation of [Ca²⁺]_i, a characteristic of store-operated Ca²⁺ channel (SOCC) activity. Two SOCC antagonists, Gd³⁺ and SKF-96365, inhibited 72±8% and 65±8% of this Ca²⁺ influx, respectively. SKF-96365 also reduced the spontaneous pacemaker rate to 27±4% of control in the presence of CPA. Because members of the transient receptor potential canonical (TRPC) gene family may encode SOCCs, we used RT-PCR to examine mRNA expression of the 7 known mammalian TRPC isoforms. Transcripts for TRPC1, 2, 3, 4, 6, and 7, but not TRPC5, were detected. Immunohistochemistry using anti-TRPC1, 3, 4, and 6 antibodies revealed positive labeling in the SAN region and single pacemaker cells. These results indicate that mouse SAN exhibits store-operated Ca²⁺ activity which may be attributable to TRPC expression, and suggest that SOCCs may be involved in regulating pacemaker firing rate.

Key Words: heart • sinoatrial node • TRPC • store-operated Ca²⁺ channel

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