Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor

Abstract

Membrane potential recordings, made from the circular smooth muscle layer of the gastric antrum taken from mutant mice which lacked the inositol trisphosphate (InsP3) type 1 receptor, were compared with those obtained from the stomach of control (wild‐type) mice. Immunostaining of gastric muscles indicated that the distribution and form of c‐kit positive cells were similar in wild‐type and mutant mice. Smooth muscles from wild‐type mice generated slow waves that in turn initiated spike potentials, while those from mutant mice were either quiescent or generated irregular bursts of spike potentials. In the presence of nifedipine, slow waves with reduced amplitude were generated in wild‐type mice, while all electrical activity was abolished in mutant mice. Acetylcholine depolarized and sodium nitroprusside hyperpolarized the membrane in muscles from both types of mice, being more effective in wild‐type mice. Noradrenaline produced similar hyperpolarizations in both types of mice. Transmural nerve stimulation evoked inhibitory junction potentials (IJPs) in both wild‐type and mutant mice. In wild‐type mice, the IJPs were reduced in amplitude by nitroarginine and converted to a cholinergic excitatory junction potential (EJP) by apamin. In mutant mice, the IJPs were unaffected by nitroarginine or atropine but were abolished by apamin. It is concluded that in antral smooth muscle, the expression of InsP3 type 1 receptors may be causally related to the generation of slow waves but not to the generation of action potentials. A lack of InsP3 receptors attenuates cholinergic excitatory and nitrergic inhibitory responses but does not alter the response to noradrenaline.

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

“…In order to find out how NaHS inhibits the pacemaker activity in ICC, we focused on [Ca 2＋ ]i. It is well known that the periodic pacemaker activity of ICC is dependent on [Ca 2＋ ]i oscillation and that this pacemaker mechanism is initiated by the release of Ca 2＋ from the endoplasmic reticulum through the inositol triphosphate (IP3) receptor followed by re-uptake of Ca 2＋ into the mitochondria [16,17]. In previous reports, we also showed the pacemaker currents were abolished in Ca 2＋ -free solution [18].…”

The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

“…receptor-operated stores in the generation of slow waves has been demonstrated pharmacologically using cultured ICCs (Ward et al, 2000), in experiments on mutant mice lacking the IP3R1 isoform of the IP3 receptor (Suzuki et al, 2000), and in pharmacological studies of intact muscle strips (Ward et al, 2000;Malysz et al, 2001). These IP3 receptors are highly expressed by ICCs and are closely associated with the plasma membrane and mitochondria.…”

Cellular Mechanisms of Myogenic Activity in Gastric Smooth Muscle.

“…In cultured chicken B [86]. In mice which genetically lack the expression of InsP 3 type-1 receptor proteins [87], gastric smooth muscle fails to produce slow waves while it keeps the ability to generate spike potentials [88,89] (Fig. 11).…”