Changes in Ca²⁺ mobilization in urinary bladder smooth muscle of ryanodine receptor type 2 heterozygous KO mouse

Abstract

Ryanodine receptor type 2 (RyR2) is thought to be the most general Ca²⁺-induced Ca²⁺ release (CICR) channel. In smooth muscle cells (SMCs), RyR2 also regulates the activity of large conductance Ca²⁺ activated K⁺ (BK) channel via CICR or spontaneous local Ca²⁺ release (Ca²⁺ spark). The contribution of RyR2 to excitation-contraction coupling and muscle tone in SM was examined using urinary bladder SMCs (UBSMCs) from RyR2 heterozygous KO mice (RyR2^+/−), in which RyR2 mRNA expression decreased by ∼50%. In resting conditions, Ca²⁺ sparks activated BK channels to elicit spontaneous transient outward currents (STOCs), and STOCs regulated resting membrane potential in UBSMs. In RyR2^+/−, the frequency of STOCs and the membrane depolarization by paxilline, a specific BK channel blocker, were significantly reduced, while BK channel expression was comparable to that in RyR2^+/+. When cells were depolarized to 0 mV, early local Ca²⁺ transients (hot spots) were observed in peripheral areas and spread into other areas of myocytes. The elevation of [Ca²⁺]i at 0 mV was significantly smaller in RyR2^+/−. The force development in tissue segments by direct electrical stimulation was also smaller in RyR2^+/−. These results strongly suggest that RyR2 play a crucial role in regulation of E-C coupling and resting tone in UBSMs. [Jpn J Physiol 55 Suppl:S122 (2005)]