Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter
- 16 January 2021
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (8), 5937-5952
- https://doi.org/10.1002/jcp.30279
Abstract
A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2‐photon imaging, and cell‐specific gene‐modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca2+ signals (i.e., synchronized Ca2+ oscillations [SCaOs] and asynchronized Ca2+ oscillations [ACaOs]) that last for hours. RyRs, TMEM16A, L‐type Ca2+ channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca2+ signals, leading to IAS's full relaxation. Our results show that the oscillating nature of Ca2+ signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.Funding Information
- Foundation for the National Institutes of Health (RO1DR098586)
This publication has 61 references indexed in Scilit:
- A New Approach for the Study of Lung Smooth Muscle Phenotypes and Its Application in a Murine Model of Allergic Airway InflammationPLOS ONE, 2013
- Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activityNature Communications, 2013
- Genetically Encoded Green Fluorescent Ca2+ Indicators with Improved Detectability for Neuronal Ca2+ SignalsPLOS ONE, 2012
- An Improved Genetically Encoded Red Fluorescent Ca2+ Indicator for Detecting Optically Evoked Action PotentialsPLOS ONE, 2012
- Anoctamin 1 (Tmem16A) Ca 2 + -activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin networkProceedings of the National Academy of Sciences of the United States of America, 2012
- Changes in neuromuscular transmission in the W/Wv mouse internal anal sphincterNeurogastroenterology & Motility, 2011
- The Dual Role of Calcium as Messenger and Stressor in Cell Damage, Death, and SurvivalInternational Journal of Cell Biology, 2010
- Regulation of the Cardiac Muscle Ryanodine Receptor by O2 Tension and S-NitrosoglutathioneBiochemistry, 2008
- A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl− Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth MuscleThe Journal of general physiology, 2008
- Ca2+ sparks activate K+ and Cl− channels, resulting in spontaneous transient currents in guinea‐pig tracheal myocytesJournal Of Physiology-London, 1998