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Stretch-induced calcium release in smooth muscle.

Ji G, Barsotti RJ, Feldman ME, Kotlikoff MI - J. Gen. Physiol. (2002)

Bottom Line: We report here that elongation of smooth muscle cells results in ryanodine receptor-mediated Ca(2+) release in individual myocytes.Thus, longitudinal stretch of smooth muscle cells induces Ca(2+) release through gating of RYR.SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

ABSTRACT
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 Ca(2+) release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to approximately 120% of slack length (DeltaL = 20) evoked Ca(2+) release from intracellular stores in the form of single Ca(2+) sparks and propagated Ca(2+) waves. Ca(2+) release was not due to calcium-induced calcium release, as release was observed in Ca(2+)-free extracellular solution and when free Ca(2+) ions in the cytosol were strongly buffered to prevent increases in [Ca(2+)](i). Stretch-induced calcium release (SICR) was not affected by inhibition of InsP(3)R-mediated Ca(2+) 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 Ca(2+) release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

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Pattern of Ca2+ release during repeated and sustained cell stretch. A–C show fluorescent profiles from x-y confocal images taken at 37.5-ms intervals; mouse myocytes were progressively stretched from slack length as shown. (A) An initial stretch elicits a burst of individual Ca2+ sparks from the same area of a cell; the sparks are not sustained, despite maintenance of the stretch. Further lengthening of the cell elicits an additional spark, indicating that the desensitization of the process does not reflect a loss of SR Ca2+. (B) Initial stretch results in a single Ca2+ spark. An additional stretch does not activate a spark, but further elongation results in multiple Ca2+ sparks of declining amplitude from the same site. (C) A large sustained stretch results in a Ca2+ wave that propagates across the cell, resulting in a sustained increase in the local Ca2+ profile.
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fig2: Pattern of Ca2+ release during repeated and sustained cell stretch. A–C show fluorescent profiles from x-y confocal images taken at 37.5-ms intervals; mouse myocytes were progressively stretched from slack length as shown. (A) An initial stretch elicits a burst of individual Ca2+ sparks from the same area of a cell; the sparks are not sustained, despite maintenance of the stretch. Further lengthening of the cell elicits an additional spark, indicating that the desensitization of the process does not reflect a loss of SR Ca2+. (B) Initial stretch results in a single Ca2+ spark. An additional stretch does not activate a spark, but further elongation results in multiple Ca2+ sparks of declining amplitude from the same site. (C) A large sustained stretch results in a Ca2+ wave that propagates across the cell, resulting in a sustained increase in the local Ca2+ profile.

Mentions: The pattern of Ca2+ release during cell elongation was also examined. Step increases in cell length were imposed to determine if Ca2+ release was sustained or accommodated, and whether Ca2+ release could be repeatedly obtained with subsequently imposed changes in cell length. Fig. 2 shows the fluorescence profiles from several experiments of this kind in which the degree and duration of length changes was varied. These experiments demonstrated that Ca2+ release was not sustained in time, but accommodated gradually during sustained cell stretch (A and B). This process did not result from a loss of Ca2+ from the SR or a complete inactivation of the underlying release process; however, since subsequent increases in cell length always resulted in additional Ca2+ release. Two possibilities could account for this pattern. First, the sensed mechanical parameter may be the change in cell length, rather than absolute tension, resulting in gating of release only during the initial phase of a step change in length. The substantial delay in some release events relative to the length change, however, seems to argue against such a mechanism. Moreover, the increased Ca2+ release with additional increases in cell length observed in some experiments (e.g., B and C) would suggest that the amount of Ca2+ release is related to wall tension. An alternative explanation for the prominent observed desensitization is that the probability of gating of Ca2+ release channels is a function of cell length and there is an inherent inactivation process for gated channels, such that a fraction of available channels are gated by the initial stretch (which inactivate) and others by subsequent increases in cell length, resulting in an accommodation of Ca2+ release at any given length.


Stretch-induced calcium release in smooth muscle.

Ji G, Barsotti RJ, Feldman ME, Kotlikoff MI - J. Gen. Physiol. (2002)

Pattern of Ca2+ release during repeated and sustained cell stretch. A–C show fluorescent profiles from x-y confocal images taken at 37.5-ms intervals; mouse myocytes were progressively stretched from slack length as shown. (A) An initial stretch elicits a burst of individual Ca2+ sparks from the same area of a cell; the sparks are not sustained, despite maintenance of the stretch. Further lengthening of the cell elicits an additional spark, indicating that the desensitization of the process does not reflect a loss of SR Ca2+. (B) Initial stretch results in a single Ca2+ spark. An additional stretch does not activate a spark, but further elongation results in multiple Ca2+ sparks of declining amplitude from the same site. (C) A large sustained stretch results in a Ca2+ wave that propagates across the cell, resulting in a sustained increase in the local Ca2+ profile.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2233869&req=5

fig2: Pattern of Ca2+ release during repeated and sustained cell stretch. A–C show fluorescent profiles from x-y confocal images taken at 37.5-ms intervals; mouse myocytes were progressively stretched from slack length as shown. (A) An initial stretch elicits a burst of individual Ca2+ sparks from the same area of a cell; the sparks are not sustained, despite maintenance of the stretch. Further lengthening of the cell elicits an additional spark, indicating that the desensitization of the process does not reflect a loss of SR Ca2+. (B) Initial stretch results in a single Ca2+ spark. An additional stretch does not activate a spark, but further elongation results in multiple Ca2+ sparks of declining amplitude from the same site. (C) A large sustained stretch results in a Ca2+ wave that propagates across the cell, resulting in a sustained increase in the local Ca2+ profile.
Mentions: The pattern of Ca2+ release during cell elongation was also examined. Step increases in cell length were imposed to determine if Ca2+ release was sustained or accommodated, and whether Ca2+ release could be repeatedly obtained with subsequently imposed changes in cell length. Fig. 2 shows the fluorescence profiles from several experiments of this kind in which the degree and duration of length changes was varied. These experiments demonstrated that Ca2+ release was not sustained in time, but accommodated gradually during sustained cell stretch (A and B). This process did not result from a loss of Ca2+ from the SR or a complete inactivation of the underlying release process; however, since subsequent increases in cell length always resulted in additional Ca2+ release. Two possibilities could account for this pattern. First, the sensed mechanical parameter may be the change in cell length, rather than absolute tension, resulting in gating of release only during the initial phase of a step change in length. The substantial delay in some release events relative to the length change, however, seems to argue against such a mechanism. Moreover, the increased Ca2+ release with additional increases in cell length observed in some experiments (e.g., B and C) would suggest that the amount of Ca2+ release is related to wall tension. An alternative explanation for the prominent observed desensitization is that the probability of gating of Ca2+ release channels is a function of cell length and there is an inherent inactivation process for gated channels, such that a fraction of available channels are gated by the initial stretch (which inactivate) and others by subsequent increases in cell length, resulting in an accommodation of Ca2+ release at any given length.

Bottom Line: We report here that elongation of smooth muscle cells results in ryanodine receptor-mediated Ca(2+) release in individual myocytes.Thus, longitudinal stretch of smooth muscle cells induces Ca(2+) release through gating of RYR.SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

ABSTRACT
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 Ca(2+) release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to approximately 120% of slack length (DeltaL = 20) evoked Ca(2+) release from intracellular stores in the form of single Ca(2+) sparks and propagated Ca(2+) waves. Ca(2+) release was not due to calcium-induced calcium release, as release was observed in Ca(2+)-free extracellular solution and when free Ca(2+) ions in the cytosol were strongly buffered to prevent increases in [Ca(2+)](i). Stretch-induced calcium release (SICR) was not affected by inhibition of InsP(3)R-mediated Ca(2+) 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 Ca(2+) release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues.

Show MeSH
Related in: MedlinePlus