Excitation-Contraction Coupling in Gastrointestinal and Other Smooth Muscles

Abstract

The main contributors to increases in [Ca2+]i and tension are the entry of Ca2+ through voltage-dependent channels opened by depolarization or during action potential (AP) or slow-wave discharge, and Ca2+ release from store sites in the cell by the action of IP3 or by Ca(2+)-induced Ca(2+)-release (CICR). The entry of Ca2+ during an AP triggers CICR from up to 20 or more subplasmalemmal store sites (seen as hot spots, using fluorescent indicators); Ca2+ waves then spread from these hot spots, which results in a rise in [Ca2+]i throughout the cell. Spontaneous transient releases of store Ca2+, previously detected as spontaneous transient outward currents (STOCs), are seen as sparks when fluorescent indicators are used. Sparks occur at certain preferred locations--frequent discharge sites (FDSs)--and these and hot spots may represent aggregations of sarcoplasmic reticulum scattered throughout the cytoplasm. Activation of receptors for excitatory signal molecules generally depolarizes the cell while it increases the production of IP3 (causing calcium store release) and diacylglycerols (which activate protein kinases). Activation of receptors for inhibitory signal molecules increases the activity of protein kinases through increases in cAMP or cGMP and often hyperpolarizes the cell. Other receptors link to tyrosine kinases, which trigger signal cascades interacting with trimeric G-protein systems.

Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra

“…Similarly, Lee & Wang (1999) reported that fenamates inhibited the voltagedependent K þ channels. The presence of 4-AP-and voltagesensitive K þ currents has been reported in a wide variety of smooth muscle (Bolton et al, 1999). In the present experiments, we were not able to detect the 4-AP-sensitive K þ channels by use of single-channel recordings, and further studies are needed to cast light upon the properties of 4-APsensitive K þ channels in pig urethra.…”

Ca2+ entry following P2X receptor activation induces IP3 receptor‐mediated Ca2+ release in myocytes from small renal arteries

“…The initial Ca 2+ mobilization may be augmented by RyR-mediated Ca 2+ release recruited via a CICR mechanism (Bolton and Gordienko, 1998;Bayguinov et al, 2000;White and McGeown, 2002;Kotlikoff, 2003;Zhang et al, 2003;Hotta et al, 2007;Gordienko et al, 2008). The contribution of these mechanisms to intracellular Ca 2+ mobilization may vary in different SMC types, depending on the type and strength of stimuli, SMC excitability and spatial organisation of intracellular Ca 2+ release units (Walsh, 1994;Bolton and Gordienko, 1998;Bolton et al, 1999;Davis and Hill, 1999;Bayguinov et al, 2000;Gordienko et al, 2001Gordienko et al, , 2008Janiak et al, 2001;Gordienko and Bolton, 2002;White and McGeown, 2002;Kotlikoff, 2003;Wier and Morgan, 2003;Zhang et al, 2003;Lamont and Wier, 2004;McCarron et al, 2006;Amberg et al, 2007;Hotta et al, 2007;Wier et al, 2009).…”

“…The initial Ca 2+ mobilization may be augmented by RyR-mediated Ca 2+ release recruited via a CICR mechanism (Bolton and Gordienko, 1998;Bayguinov et al, 2000;White and McGeown, 2002;Kotlikoff, 2003;Zhang et al, 2003;Hotta et al, 2007;Gordienko et al, 2008). The contribution of these mechanisms to intracellular Ca 2+ mobilization may vary in different SMC types, depending on the type and strength of stimuli, SMC excitability and spatial organisation of intracellular Ca 2+ release units (Walsh, 1994;Bolton and Gordienko, 1998;Bolton et al, 1999;Davis and Hill, 1999;Bayguinov et al, 2000;Gordienko et al, 2001Gordienko et al, , 2008Janiak et al, 2001;Gordienko and Bolton, 2002;White and McGeown, 2002;Kotlikoff, 2003;Wier and Morgan, 2003;Zhang et al, 2003;Lamont and Wier, 2004;McCarron et al, 2006;Amberg et al, 2007;Hotta et al, 2007;Wier et al, 2009).We hypothesized that in vascular myocytes Ca 2+ entry following activation of ionotropic P2X receptors may induce IP3R-mediated Ca 2+ release. Our hypothesis was based on the following findings reported in visceral and vascular myocytes: (i) a localized increase in [Ca 2+ ]i induced by local flash release of Ca 2+ from a 'caged' precursor may trigger IP3R-mediated Ca 2+ release (Ji et al, 2006); (ii) Ca 2+ entry via VGCCs facilitates IP3R-mediated Ca 2+ release following stimulation of metabotropic receptors (Gordienko et al, 2008); (iii) the stoichiometric ratio of RyRs to IP3Rs in SMCs is 1:9-10, suggesting the existence of a Ca 2+ -storage compartment devoid of RyRs but equipped with IP3Rs (Wibo and Godfraind, 1994); (iv) caffeine/ryanodinereleasable and IP3-releasable calcium stores in the SR of vascular myocytes are at least partially distinct with about 56% of the SR being solely IP3-sensitive (Blauste...…”

The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema

“…2+ levels regulate a plethora of intracellular processes, among them smooth muscle contraction [14] and vascular permeability [15]. The Ca 2+ signals are sensed by calcium-binding proteins, of which calmodulin is the most important.…”