An essential role of Cav1.2 L‐type calcium channel for urinary bladder function

Abstract

Mice deficient in the smooth muscle Ca_v1.2 calcium channel (SMACKO, smooth muscle α_1c‐ subunit calcium channel knockout) have a severely reduced micturition and an increased bladder mass. L‐type calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K⁺ and carbachol (CCh)‐induced contractions were reduced to 10‐ fold in detrusor muscles from SMACKO mice. The dihydropyridine isradipine inhibited K⁺‐ and CCh‐induced contractions of muscles from CTR but had no effect in muscles from SMACKO mice. CCh‐induced contraction was blocked by removing extracellular Ca²⁺ but was unaffected by the PLC inhibitor U73122 or depletion of intracellular Ca²⁺ stores by thapsigargin. In muscles from CTR and SMACKO mice, CCh‐induced contraction was partially inhibited by the Rho‐ kinase inhibitor Y27632. These results show that the Ca_v1.2 Ca²⁺ channel is essential for normal bladder function. The Rho‐kinase and Ca²⁺‐release pathways cannot compensate the lack of the L‐type Ca²⁺ channel.