Muscarinic Receptor Induced Contractions of the Detrusor are Mediated by Activation of TRPC4 Channels

Purpose: Muscarinic receptor mediated contractions of the detrusor rely on Ca2+ influx through voltage-gated Ca2+ channels but to our knowledge the mechanism linking stimulation of M3Rs to the activation of voltage dependent Ca2+ channels has not been established. TRPC4 channels are receptor operated cation channels that couple muscarinic receptor activation to depolarization of intestinal smooth muscle cells, voltage-activated Ca2+ influx and contraction. We investigated whether TRPC4 channels are involved in cholinergic mediated contractions of the detrusor.Materials and Methods: Isometric tension recordings were made on strips of murine detrusor and intracellular Ca2+ measurements were made on isolated detrusor myocytes using confocal microscopy. Transcriptional expression of TRPC and IP3R subtypes in intact detrusor strips and isolated detrusor myocytes was assessed using reverse transcriptase-polymerase chain reaction.Results: Cholinergic stimulation of the detrusor induced by electrical field stimul...