Control of intestinal motility by the Cav1.2 L‐type calcium channel in mice

Abstract

The Ca_v1.2 L-type Ca²⁺ channel is the dominant voltage-activated Ca²⁺ channel in heart and smooth muscle. The functional significance of this channel was studied in intestinal smooth muscle from mice carrying a smooth muscle-specific, conditional inactivation of the Ca_v1.2 gene (Ca_v1.2^SMACKO mice). Inactivation was complete within 4 wk after tamoxifen treatment and confirmed by RT-PCR, Western blot and functional analysis. Ca_v1.2^SMACKO mice show reduced feces excretion, absence of rhythmic contractions in small and large intestinal muscle and signs of paralytic ileus. Extracellular field stimulation evoked smaller contractions in jejunum muscles from Ca_v1.2^SMACKO than from CTR mice, whereas carbachol-induced contractions of similar magnitude in both muscles. The Ca²⁺ needed for contraction in jejunum was provided mainly by Ca_v1.2 channels and by store-operated channels in muscles from CTR and Ca_v1.2^SMACKO mice, respectively. In conclusion, the Ca_v1.2 channel is essential for electromechanical coupling and important for pharmaco-mechanical coupling in intestinal smooth muscle and cannot be substituted functionally by other Ca²⁺ entry pathways.—Wegener, J. W., Schulla, V., Koller, A., Klugbauer, N., Feil, R., Hofmann, F. Control of intestinal motility by the Ca_v1.2 L-type calcium channel in mice.