Store-operated Ca2+ influx and expression of TRPC genes in mouse sinoatrial node.
Circ Res
; 100(11): 1605-14, 2007 Jun 08.
Article
en En
| MEDLINE
| ID: mdl-17478725
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.
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Bases de datos:
MEDLINE
Asunto principal:
Nodo Sinoatrial
/
Relojes Biológicos
/
Canales de Calcio
/
Calcio
/
Señalización del Calcio
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Canales Catiónicos TRPC
Límite:
Animals
Idioma:
En
Revista:
Circ Res
Año:
2007
Tipo del documento:
Article
País de afiliación:
Australia