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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 582/2/489    most recent jphysiol.2007.130302v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hotta, S. Articles by Imaizumi, Y. Search for Related Content PubMed PubMed Citation Articles by Hotta, S. Articles by Imaizumi, Y. Related Collections Cellular

¹ Department of Molecular and Cellular Pharmacology Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya, Japan
² Cell Signalling & Ion Channel Research Group, Cellular Pharmacology, School of Pharmacy, Aichigakuin University, Nagoya, Japan
³ Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan

The possibility that the ryanodine receptor type 2 (RyR2) can function as the major Ca²⁺-induced Ca²⁺ release (CICR) channel in excitation–contraction (E-C) coupling was examined in smooth muscle cells (SMCs) isolated from urinary bladder (UB) of RyR2 heterozygous KO mice (RyR2+^/–). RyR2 mRNA expression in UB from RyR2+^/– was much lower than that in wild-type (RyR2^plus;/plus;). In single UBSMCs from RyR2^plus;/+, membrane depolarization under voltage clamp initially induced several local Ca²⁺ transients (hot spots) in peripheral areas of the cell. Then, Ca²⁺ waves spread from Ca²⁺ hot spots to other areas of the myocyte. The number of Ca²⁺ hot spots elicited by a short depolarization (< 20 ms) in UBSMCs of RyR2+^/– was significantly smaller than in those of RyR2^+/+. The force development induced either by direct electrical stimulation or by 10 µM acetylcholine in tissue segments of RyR2+^/– was smaller than and comparable to those in RyR2^+/+, respectively. The frequency of spontaneous transient outward currents in single myocytes and the membrane depolarization by 1 µM paxilline in tissue segments from RyR2^+/– were significantly lower and smaller than those in RyR2^+/+, respectively. The urination frequency and volume per voiding in RyR2^+/– were significantly increased and reduced, respectively, compared with RyR2^+/+. In conclusion, RyR2 plays a crucial role in the regulation of CICR during E-C coupling and also in the regulation of resting membrane potential, presumably via the modulation of Ca²⁺-dependent K⁺ channel activity in UBSMCs and, thereby, has a pivotal role in the control of bladder activity.

(Received 11 February 2007; accepted after revision 8 March 2007; first published online 15 March 2007)
Corresponding author Y. Imaizumi: Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Science, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan. Email: yimaizum{at}phar.nagoya-cu.ac.jp

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