Ca2+ sparks

Ca2+ sparks are localized and transient Ca2+ release observed recurrently in muscle cells and skinned fibres. A Ca2+ spark is considered to be the elementary process of Ca2+ release in situ from one to a few ryanodine receptors. 

Recent work using confocal microscopy has found localized increases of [Ca2+]j named Ca2+ sparks which are due to the release of Ca2+ from one or a small number of RyRs (Jaggar et al 2000). These localized releases of Ca2+ activate Ca2+-dependent channels in the surface membrane (Perez et al 2001). Activation of the Ca2+-activated K+ current will hyperpolarize the membrane potential (Herrera et al 2001) and thereby decrease Ca2+ entry into the cell on voltage-dependent Ca2+ channels. This provides a mechanism whereby Ca2+ release from the SR can decrease contraction. It is therefore important, in different smooth muscles, to consider to what extent SR Ca2+ release activates rather than decreases contraction. It is, of course, possible that, in the same smooth muscle, SR release may sometimes directly activate contraction and, at other times, decrease it by activating K+ channels. 

Herrera GM, Heppner TJ, Nelson MT 2001 Voltage dependence of the coupling of Ca2+ sparks to BKCa channels in urinary bladder smooth muscle. Am J Physiol Cell Physiol 280 ... 

There have been no reports of sparks occurring in uterine cells. Ca2+ sparks are considered to be due to spontaneous releases of Ca2+ from RyR. 

ZhuGe R, Tuft RA, Fogarty KE, Bellve K, Fay FS, Walsh JV 1999 The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and spontaneous transient outward currents in single smooth muscle cells. J Gen Physiol 113 215—228... 

Wier I think you showed that voltage depolarization in smooth muscle increased the frequency of Ca2+ sparks. What you are asserting is that this was not local control that it was just due to an elevation of cytoplasmic and SR... 

Gordienko D V, Greenwood IA, Bolton TB 2001 Direct visualization of sarcoplasmic reticulum regions discharging Ca2+ sparks in vascular myocytes. Cell Calcium 29 13-28... 

Mauban JRH, Lamont C, Balke CW, Wier WG 2001 Adrenergic stimulation of rat resistance arteries affects Ca2+ sparks, Ca2+ waves, and Ca2+ oscillations. Am 1 Physiol 280 H2399— H2405... 

Bonev AD, Jaggar JH, Rubart M, Nelson MT 1997 Activators of protein kinase C decrease Ca2+ spark frequency in smooth muscle cells from cerebral arteries. Am J Physiol Cell Physiol... 

FIG. 2. Ca2+ channels can open without activating Ca2+ sparks. Individual sparks are not evoked with very brief depolarizations to activate ICa. With longer depolarizations, delayed Ca2+ sparks (middle panels) or a propagated wave (far right panel) are evoked. X—T linescan image is shown above, voltage and current, below. (From Collier et al 2000.)... 

EGTA and I l uo 4 and simultaneous recordings of Iq, and Ca2+ fluorescence were made. As expected for tight coupling in cardiac myocytes, brief Ca2+ sparks were recorded following activation of Iya (Fig. 3). Conversely, however, coupling between L-type Ca2+ channels and RyRs was completely abrogated in bladder myocytes recorded under identical conditions. 

Ca2+ sparks (Ji et al 2002). Single Ca2+ sparks with kinetics quite similar to spontaneous events are evoked from FDSs following moderate stretch of cells to about 20% of its resting length, by means of two pipettes attached at each end of the cell. In these experiments, stretch-induced Ca2+ sparks occur from the same sites as those at which spontaneous Ca2+ sparks are observed before the application of stretch. Equivalent results have been obtained from mouse urinary bladder myocytes, indicating that stretch-induced Ca2+ release (SICR) may be a widespread phenomenon. 

FIG. 5. Ca2+ sparks drive electrical activity in myocytes. In contrast to the traditional concept of electrical activity deriving from descending neural control via postsynaptic responses, spontaneous Ca2+ release results in electrical activity in smooth muscle. The figure shows a Ca2+ spark activating sarcolemmal Ca2+-activated Cl- channels and spontaneous transient inward currents (STICs) (current trace above). Whether Ca2+ sparks activate outward STOCs (Ca2+-activated K+ currents) or STICs will depend on the proportion of channels expressed and the resting potential of the myocyte. 

Gordienko DV, Greenwood IA, Bolton TB 2001 Direct visualization of sarcoplasmic reticulum regions discharging Ca2+ sparks in vascular myocytes. Cell Calcium 29 13—28 Imaizumi Y, Torii Y, Ohi Y et al 1998 Ca2+ images and K+ current during depolarization in smooth muscle cells of the guinea-pig vas deferens and urinary bladder. J Physiol (Lond) 510 705-719... 

Mironneau J, Arnaudeau S, Macrez-Lepretre N, Boittin FX 1996 Ca2+ sparks and Ca2+ waves activate different Ca2+-dependent ion channels in single myocytes from rat portal vein. Cell Calcium 20 153—160... 

Wier WG, ter Keurs HE, Marban E, Gao WD, Balke CW 1997 Ca2+ sparks and waves in intact ventricular muscle resolved by confocal imaging. Circ Res 81 462-469... 

ZhuGe R, Sims SM, Tuft RA, Fogarty KE, Walsh JV Jr 1998 Ca2+ sparks activate K+ and Cl-channels, resulting in spontaneous transient currents in guinea-pig tracheal myocytes. J Physiol (London) 513 711-718... 

Nelson We have examined sparks in pressurized arteries. The effects of pressure on Ca2+ sparks appear to be the result of changes in intracellular Ca2+. pH changes RyR open probability alkalinization increases it. One thing I would look at is whether any of the manoeuvres cause alkalinization. 

Sanders So what you are saying is that the resting potential is sitting in a situation where the Ca2+ sparks are preferentially activating outward currents, not inward currents. 

An initial hint that Ca2+ stores are present and functional in smooth muscle cells came from earlier experiments revealing that agonist-induced contractions could be observed in the absence of extracellular Ca2+. It is now known that smooth muscle Ca2+ stores express two types of Ca2+ release channels, the ryanodine receptor (RyR) and the inositol-1,4,5-trisphosphate (L1SP3) receptor (L1SP3R) (Somlyo Somlyo 1994). Recent studies have shown that Ca2+ release from intracellular Ca2+ stores plays various important roles in the regulation of smooth muscle contraction. Local and transient releases of Ca2+ from RyR near the surface membrane, which are called Ca2+ sparks, activate Ca2+-sensitive K+... 

Porter VA, Bonev AD, Knot HJ et al 1998 Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides. Am J Physiol 274 C1346—C1355 Pucovsky V, Gordienko D V, Bolton TB 2002 Effect of nitric oxide donors and noradrenaline on Ca2+ release sites and global intracellular Ca2+ in myocytes from guinea-pig small mesenteric arteries. J Physiol 539 25—39... 

ZhuGe R, Fogarty KE, Tuft RA, Lifshitz LM, Sayar K, Walsh JV 2000 Dynamics of signaling between Ca2+ sparks and Ca2+-activated K+ channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca2+ current. J Gen... 

To date, all smooth muscle types examined display characteristic Ca2+ release events known as Ca2+ sparks (Fig. 1 see Jaggar et al 2000 for review). Ca2+ sparks are localized Ca2+ release events through RyRs in the SR located very close (10—20nm) to the surface membrane. Ca2+ sparks can activate Ca2+ -dependent ion channels in the cell surface, and the physiological response of the particular cell type will reflect the type of ion channels involved (Fig. 1). 

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