Inositol 1,4,5-trisphosphate receptors modulate Ca²⁺ sparks and Ca²⁺ store content in vas deferens myocytes

Abstract

White, Carl, and J. Graham McGeown. Inositol 1,4,5-trisphosphate receptors modulate Ca 2ϩ sparks and Ca 2ϩ store content in vas deferens myocytes. Am J Physiol Cell Physiol 285: C195-C204, 2003. First published March 5, 2003 10.1152/ajpcell.00374.2002 sparks were observed in fluo 4-loaded myocytes from guinea pig vas deferens with line-scan confocal imaging. They were abolished by ryanodine (100 M), but the inositol 1,4,5-trisphosphate (IP 3) receptor (IP3R) blockers 2-aminoethoxydiphenyl borate (2-APB; 100 M) and intracellular heparin (5 mg/ml) increased spark frequency, rise time, duration, and spread. Very prolonged Ca 2ϩ release events were also observed in ϳ20% of cells treated with IP 3R blockers but not under control conditions. 2-APB and heparin abolished norepinephrine (10 M; 0 Ca 2ϩ )-evoked Ca 2ϩ transients but increased caffeine (10 mM; 0 Ca 2ϩ ) transients in fura 2-loaded myocytes. Transients evoked by ionomycin (25 M; 0 Ca 2ϩ ) were also enhanced by 2-APB. Ca 2ϩ sparks and transients evoked by norepinephrine and caffeine were abolished by thimerosal (100 M), which sensitizes the IP 3R to IP3. In cells voltage clamped at Ϫ40 mV, spontaneous transient outward currents (STOCs) were increased in frequency, amplitude, and duration in the presence of 2-APB. These data are consistent with a model in which the Ca 2ϩ store content in smooth muscle is limited by tonic release of Ca 2ϩ via an IP3-dependent pathway. Blockade of IP 3Rs elevates sarcoplasmic reticulum store content, promoting Ca 2ϩ sparks and STOC activity. calcium ion release; calcium ion transients; smooth muscle IT IS WELL ESTABLISHED THAT release of Ca 2ϩ from the sarcoplasmic reticulum (SR) can be evoked by activating receptors sensitive to inositol 1,4,5-trisphosphate (IP 3 Rs) or ryanodine (RyRs) (2). The resulting Ca 2ϩ signal may be generalized or restricted to a specific region of the cell. Transient, local release events known as "Ca 2ϩ sparks" are generated by the spontaneous opening of a cluster of RyR channels (3, 15). These sparks represent fundamental signaling events whose spatial and temporal summation generates global increases in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) during excitation-contraction coupling in cardiac and skeletal muscle (6,29). In smooth muscle sparks may also modulate membrane conductances (for review see Ref. 14), either opening Ca 2ϩ -activated Cl Ϫ channels to cause depolarization and contraction (40) or promoting relaxation by activating large-conductance Ca 2ϩ -activated K ϩ channels and so hyperpolarizing the membrane (24, 41). Understanding the control of Ca 2ϩ spark activity is crucial, therefore, to our understanding of smooth muscle function.The [Ca 2ϩ ] within the cytosol and the SR lumen may both play an important role in spark modulation. An elevation in [Ca 2ϩ ] i increases the open probability of the RyR channel, increasing the frequency of Ca 2ϩ sparks (7), whereas changes in the SR load can affect both spark frequency and amplitude (41). The filling state of the SR must reflect...

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Inositol 1,4,5-Trisphosphate Signaling Regulates Mating Behavior inCaenorhabditis elegansMales

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