Control of intestinal motility by the Ca(v)1.2 L-type calcium channel in mice.
The Ca(v)1.2 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(v)1.2 gene (Ca(v)1.2SMACKO mice). Inactivation was complete within 4 wk after tamoxifen treatment and confirmed by RT-PCR, Western blot and functional analysis. Ca(v)1.2SMACKO 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(v)1.2SMACKO 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(v)1.2 channels and by store-operated channels in muscles from CTR and Ca(v)1.2SMACKO mice, respectively. In conclusion, the Ca(v)1.2 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
Jörg W
JW
Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, München 80802, Germany. wegener@ipt.med.tu-muenchen.de
Schulla
Verena
V
Koller
Angela
A
Klugbauer
Norbert
N
Feil
Robert
R
Hofmann
Franz
F
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005769:Gastrointestinal Motility; D007422:Intestines / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology
D020746:Calcium Channels, L-Type; D018679:Cholinergic Agonists; C419385:L-type calcium channel alpha(1C); D002217:Carbachol