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Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
VIP and PACAP regulate localized Ca2+ transients via cAMP-dependent mechanism
Brian M Hagen1, Orline Bayguinov, Kenton M Sanders
1Dept. of Physiology and Cell Biology, Univ. of Nevada School of Medicine, Reno, NV 89557-0046, USA.
American Journal of Physiology. Cell Physiology
|March 31, 2006
Summary
Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) regulate gastrointestinal motility by increasing calcium transients and outward currents in colonic smooth muscle cells. This mechanism involves adenylyl cyclase, cAMP, and PKA-dependent pathways.
Area of Science:
- Gastroenterology
- Neuroscience
- Cell Physiology
Background:
- Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are implicated in the neural regulation of gastrointestinal motility.
- These peptides induce postjunctional effects like hyperpolarization and contraction inhibition in smooth muscle cells.
- Enteric neuropeptides can directly stimulate smooth muscle, unlike synaptic transmitters.
Purpose of the Study:
- To investigate the cellular mechanisms by which VIP and PACAP influence murine colonic smooth muscle cells.
- To elucidate the role of calcium (Ca2+) transients and spontaneous transient outward currents (STOCs) in mediating the effects of these peptides.
Main Methods:
- Confocal microscopy and patch-clamp electrophysiology were used to study isolated murine colonic myocytes.
- Responses to VIP, PACAP(1-38), dibutyryl cAMP, and specific inhibitors were analyzed.
Main Results:
- VIP and PACAP increased the frequency and amplitude of localized Ca2+ transients (Ca2+ puffs) and STOCs in colonic myocytes.
- Dibutyryl cAMP mimicked these effects, suggesting a role for cyclic AMP (cAMP).
- Adenylyl cyclase and A-kinase-anchoring protein (AKAP) inhibition blocked VIP/PACAP-induced responses, while ryanodine receptor inhibition blocked cAMP effects.
Conclusions:
- VIP and PACAP modulate colonic smooth muscle activity through Ca2+ transients that activate STOCs.
- The mechanism involves adenylyl cyclase activation, increased cAMP synthesis, and PKA-dependent regulation of ryanodine receptor channels.
- These findings highlight a novel pathway for VIP and PACAP in regulating gastrointestinal motility.
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