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¹ Department of Biomedical Sciences College of Veterinary Medicine Cornell University, Ithaca, NY 14853
² Department of Pathology, Anatomy, and Cell Biology Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107

Address correspondence to Michael I. Kotlikoff, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, T4018 VRT, Box 11, Ithaca, NY 14853-6401. Fax: (607) 253-3317; E-mail: mik7{at}cornell.edu

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca²⁺ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to 120% of slack length (L = 20) evoked Ca²⁺ release from intracellular stores in the form of single Ca²⁺ sparks and propagated Ca²⁺ waves. Ca²⁺ release was not due to calcium-induced calcium release, as release was observed in Ca²⁺-free extracellular solution and when free Ca²⁺ ions in the cytosol were strongly buffered to prevent increases in [Ca²⁺]_i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP₃R-mediated Ca²⁺ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca²⁺ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

Key Words: ryanodine receptor • Ca²⁺ sparks • calcium-activated chloride current • cation current • sarcoplasmic reticulum

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