Muscarinic effects on ion channels in smooth muscle cells

Zholos, Alexander

doi:10.1007/bf02515064

Cited by 7 publications

(7 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, activation of M 2 receptors is coupled via PTX-sensitive G proteins (G i ) to inhibition of adenylyl cyclase activity [63, 66] leading to a decrease in cAMP level and, as a result, to suppression of the inhibitory effects of protein kinase A on the PLCβ – IP 3 – IP 3 R signalling pathway [67, 68]. Finally, activation of muscarinic receptors produces excitation of gastro-intestinal (GI) smooth muscles causing depolarization of SMCs and an increase in the frequency of the action potentials via modulation of the activity of many different channel types (reviewed in [64, 69; 70]), of which opening of the cationic channels [35; 71] synergistically regulated via M 2 – G αo [37; 72, 73] and/or M 2 /M 3 – G o – atypical PLC [64, 74-76] and M 3 – G q/11 – PLCβ – IP 3 – Ca 2+ [24, 26, 27; 35-37] pathways is one of the major mechanisms of GI smooth muscle excitation. The inward Na + current through muscarinic cationic channels (in many smooth muscles, including guinea-pig ileum, these channels have very low, if any, permeability to Ca 2+ [25-27], see also Figs.…”

Section: Discussionmentioning

confidence: 99%

Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+ release induced by voltage-gated Ca2+ entry

et al. 2008

View full text Add to dashboard Cite

Membrane depolarization triggers Ca2+ release from the sarcoplasmic reticulum (SR) in skeletal muscles via direct interaction between the voltage-gated L-type Ca2+ channels (the dihydropyridine receptors; VGCCs) and ryanodine receptors (RyRs), while in cardiac muscles Ca2+ entry through VGCCs triggers RyR-mediated Ca2+ release via a Ca2+-induced Ca2+ release (CICR) mechanism. Here we demonstrate that in phasic smooth muscle of the guinea-pig small intestine, excitation evoked by muscarinic receptor activation triggers an abrupt Ca2+ release from sub-plasmalemmal (sub-PM) SR elements enriched with inositol 1,4,5-trisphosphate receptors (IP3Rs) and poor in RyRs. This was followed by a lesser rise, or oscillations in [Ca2+]i. The initial abrupt sub-PM [Ca2+]i upstroke was all but abolished by block of VGCCs (by 5 μM nicardipine), depletion of intracellular Ca2+ stores (with 10 μM cyclopiazonic acid) or inhibition of IP3Rs (by 2 μM xestospongin C or 30 μM 2-APB), but was not affected by block of RyRs (by 50–100 μM tetracaine or 100 μM ryanodine). Inhibition of either IP3Rs or RyRs attenuated phasic muscarinic contraction by 73%. Thus, in contrast to cardiac muscles, excitation–contraction coupling in this phasic visceral smooth muscle occurs by Ca2+ entry through VGCCs which evokes an initial IP3R-mediated Ca2+ release activated via a CICR mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+ release induced by voltage-gated Ca2+ entry

et al. 2008

View full text Add to dashboard Cite

show abstract

“…More recently, multiple muscarinic ion channel effects have been described in voltage-clamped cells, which include generation of inward cationic or chloride current, inhibition or potentiation of voltage-dependent Ca 2+ current, and modulation of several types of K + currents (reviewed in detail elsewhere [3,5,6,36,37] ).…”

Section: Muscarinic Effects On Ion Channels In Gi Smooth Musclesmentioning

confidence: 99%

“…As both types of channels are [Ca 2+ ] i -sensitive they were proposed to be involved in a positive feedback loop whereby Ca 2+ entry and Ca 2+ release promote membrane depolarization and further Ca 2+ influx [38,39] , termed Ca 2+ -induced Ca 2+ entry [40] . This action might be further facilitated by the muscarinic inhibition of several types of K + channels, such as BK Ca , delayed rectifier and K ATP channels [37] . There are also mechanisms that provide negative feedback control by either limiting (VDCC channel inhibition, mI CAT desensitization) or terminating (BK Ca activation) cholinergic membrane depolarization.…”

Section: Muscarinic Effects On Ion Channels In Gi Smooth Musclesmentioning

confidence: 99%

Regulation of TRP-like muscarinic cation current in gastrointestinal smooth muscle with special reference to PLC/InsP3/Ca2+ system

Zholos

2006

Acta Pharmacologica Sinica

View full text Add to dashboard Cite

Acetylcholine, the main enteric excitatory neuromuscular transmitter, evokes membrane depolarization and contraction of gastrointestinal smooth muscle cells by activating G protein-coupled muscarinic receptors. Although the cholinergic excitation is generally underlined by the multiplicity of ion channel effects, the primary event appears to be the opening of cation-selective channels; among them the 60 pS channel has been recently identified as the main target for the acetylcholine action in gastrointestinal myocytes. The evoked cation current, termed mI CAT , causes either an oscillatory or a more sustained membrane depolarization response, which in turn leads to increases of the open probability of voltage-gated Ca 2+ channels, thus providing Ca 2+ entry in parallel with Ca 2+ release for intracellular Ca 2+ concentration rise and contraction. In recent years there have been several significant developments in our understanding of the signaling processes underlying mI CAT generation. They have revealed important synergistic interactions between M 2 and M 3 receptor subtypes, single channel mechanisms, and the involvement of TRPC-encoded proteins as essential components of native muscarinic cation channels. This review summarizes these recent findings and in particular discusses the roles of the phospholipase C/InsP 3 /intracellular Ca 2+ release system in the mI CAT physiological regulation.

show abstract

“…Multiple effects of mAChR activation on ion channels have been described in gastrointestinal and other visceral smooth muscles, including activation of non-selective cationic channels or chloride (Cl − ) channels, inhibition or potentiation of voltage-dependent Ca 2+ channels (VDCCs) and modulation of several K + channel types [ 12 , 14 , 29 , 30 ]. These effects underlie muscarinic modulation of smooth muscle excitation and contraction, as evidenced by recent studies of ileal longitudinal smooth muscle cells from various mAChR-KO mice.…”

Section: Muscarinic Regulation Of Ion Channel Activitymentioning

confidence: 99%

“…Chloride channels are expressed in many smooth muscles and contribute to depolarisation, as the Cl − equilibrium potential is well above the resting potential [ 30 ]. Like BK channels, chloride channel opening is triggered by intracellular Ca 2+ release.…”

Section: Muscarinic Regulation Of Ion Channel Activitymentioning

confidence: 99%

Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

Tanahashi

Komori

Matsuyama

et al. 2021

IJMS

View full text Add to dashboard Cite

Parasympathetic signalling via muscarinic acetylcholine receptors (mAChRs) regulates gastrointestinal smooth muscle function. In most instances, the mAChR population in smooth muscle consists mainly of M2 and M3 subtypes in a roughly 80% to 20% mixture. Stimulation of these mAChRs triggers a complex array of biochemical and electrical events in the cell via associated G proteins, leading to smooth muscle contraction and facilitating gastrointestinal motility. Major signalling events induced by mAChRs include adenylyl cyclase inhibition, phosphoinositide hydrolysis, intracellular Ca2+ mobilisation, myofilament Ca2+ sensitisation, generation of non-selective cationic and chloride currents, K+ current modulation, inhibition or potentiation of voltage-dependent Ca2+ currents and membrane depolarisation. A lack of ligands with a high degree of receptor subtype selectivity and the frequent contribution of multiple receptor subtypes to responses in the same cell type have hampered studies on the signal transduction mechanisms and functions of individual mAChR subtypes. Therefore, novel strategies such as genetic manipulation are required to elucidate both the contributions of specific AChR subtypes to smooth muscle function and the underlying molecular mechanisms. In this article, we review recent studies on muscarinic function in gastrointestinal smooth muscle using mAChR subtype-knockout mice.

show abstract

Muscarinic effects on ion channels in smooth muscle cells

Cited by 7 publications

References 99 publications

Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+ release induced by voltage-gated Ca2+ entry

Sub-plasmalemmal [Ca2+]i upstroke in myocytes of the guinea-pig small intestine evoked by muscarinic stimulation: IP3R-mediated Ca2+ release induced by voltage-gated Ca2+ entry

Regulation of TRP-like muscarinic cation current in gastrointestinal smooth muscle with special reference to PLC/InsP3/Ca2+ system

Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

Contact Info

Product

Resources

About