Evidence for altered circular smooth muscle cell function in lower esophageal sphincter of W/Wv mutant mice

Area of Science:

• Gastroenterology
• Physiology
• Cell Biology

Background:

• Nitrergic neurotransmission to gut smooth muscle is impaired in W/W(v) mutant mice lacking intramuscular interstitial cells of Cajal (ICC-IM).
• These mice exhibit smaller amplitude unitary potentials (UPs) and a more negative resting membrane potential (RMP).
• Previous studies attributed these abnormalities to the absence of ICC-IM, but intrinsic smooth muscle alterations were also possible.

Purpose of the Study:

• To investigate whether circular smooth muscle (CSM) cells from the lower esophageal sphincter (LES) of W/W(v) mutant mice exhibit intrinsic functional abnormalities.
• To compare electrophysiological and calcium signaling properties of CSM cells from W/W(v) mutant and control mice.

Main Methods:

• Amphotericin-B-perforated patch-clamp recordings were used to assess RMP, UPs, and responses to stimuli.
• Calcium imaging (fura 2) was employed to evaluate intracellular calcium transients.
• CSM cells were isolated from the LES of W/W(v) mutant and control mice.

Main Results:

• CSM cells from W/W(v) mutant mice had a more negative RMP and significantly smaller UPs compared to controls.
• Caffeine induced a larger inward current density in mutant CSM cells.
• Sodium nitroprusside-induced hyperpolarization was reduced in mutant CSM cells, and intracellular Ca(2+) transients induced by caffeine were increased.

Conclusions:

• LES CSM cells in W/W(v) mutant mice display intrinsic abnormalities.
• These findings challenge the sole attribution of previously observed physiological dysfunctions to the absence of ICC-IM.
• Reconsideration of physiological functions attributed to ICC-IM in ICC-deficient mice is warranted.