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Stretch-induced calcium release in smooth muscle
Guangju Ji1, Robert J Barsotti, Morris E Feldman
1Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
The Journal of General Physiology
|May 30, 2002
Summary
Mechanical stretch of smooth muscle cells triggers calcium release via ryanodine receptors (RYR). This stretch-induced calcium release (SICR) occurs independently of external calcium and may regulate spontaneous currents in smooth muscle.
Area of Science:
- Physiology
- Cell Biology
- Smooth Muscle Physiology
Background:
- Smooth muscle cells passively lengthen under increased pressure in hollow organs.
- Active contractile responses to pressure changes are known but mechanisms are debated.
- Previous research has not fully elucidated the role of intracellular calcium signaling in smooth muscle stretch responses.
Purpose of the Study:
- To investigate the mechanism of calcium release in smooth muscle cells upon mechanical elongation.
- To determine the role of ryanodine receptors (RYR) and inositol trisphosphate receptors (InsP3R) in stretch-induced calcium release (SICR).
- To explore the relationship between SICR and stretch-activated currents in smooth muscle cells.
Main Methods:
- Mechanical elongation of isolated single urinary bladder smooth muscle cells.
- Measurement of intracellular calcium (Ca2+) release using fluorescent indicators.
- Application of pharmacological inhibitors (ryanodine, InsP3R inhibitors) and manipulation of extracellular/cytosolic calcium concentrations.
- Recording of ionic currents in smooth muscle cells.
Main Results:
- Mechanical stretch induced Ca2+ release from intracellular stores in the form of Ca2+ sparks and waves.
- Stretch-induced calcium release (SICR) was independent of extracellular calcium and cytosolic calcium buffering, ruling out calcium-induced calcium release.
- SICR was blocked by ryanodine but unaffected by InsP3R inhibition, indicating RYR-mediated release.
- SICR occurred without stretch-activated currents but evoked calcium-activated chloride currents.
- SICR was also observed in intact urinary bladder smooth muscle segments.
Conclusions:
- Longitudinal stretch of smooth muscle cells directly gates ryanodine receptors (RYR), leading to calcium release.
- Stretch-induced calcium release (SICR) is a distinct mechanism from calcium-induced calcium release and InsP3R-mediated release.
- SICR may play a significant role in the physiological response of smooth muscle to increased luminal pressure and in generating spontaneous currents.