First Author | Hotta S | Year | 2007 |
Journal | J Physiol | Volume | 582 |
Issue | Pt 2 | Pages | 489-506 |
PubMed ID | 17363382 | Mgi Jnum | J:151738 |
Mgi Id | MGI:4355127 | Doi | 10.1113/jphysiol.2007.130302 |
Citation | Hotta S, et al. (2007) Ryanodine receptor type 2 deficiency changes excitation-contraction coupling and membrane potential in urinary bladder smooth muscle. J Physiol 582(Pt 2):489-506 |
abstractText | The possibility that the ryanodine receptor type 2 (RyR2) can function as the major Ca(2+)-induced Ca(2+) 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+/+. In single UBSMCs from RyR2+/+, membrane depolarization under voltage clamp initially induced several local Ca(2+) transients (hot spots) in peripheral areas of the cell. Then, Ca(2+) waves spread from Ca(2+) hot spots to other areas of the myocyte. The number of Ca(2+) 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 microm 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 microm 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 Ca(2+)-dependent K(+) channel activity in UBSMCs and, thereby, has a pivotal role in the control of bladder activity. |