Affiliation:
1. 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.
Abstract
Store-operated Ca
2+
entry was investigated in isolated mouse sinoatrial nodes (SAN) dissected from right atria and loaded with Ca
2+
indicators. Incubation of the SAN in Ca
2+
-free solution caused a substantial decrease in resting intracellular Ca
2+
concentration ([Ca
2+
]
i
) and stopped pacemaker activity. Reintroduction of Ca
2+
in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca
2+
pump inhibitor, led to sustained elevation of [Ca
2+
]
i
, a characteristic of store-operated Ca
2+
channel (SOCC) activity. Two SOCC antagonists, Gd
3+
and SKF-96365, inhibited 72±8% and 65±8% of this Ca
2+
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 Ca
2+
activity which may be attributable to TRPC expression, and suggest that SOCCs may be involved in regulating pacemaker firing rate.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
112 articles.
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