Modulation of carbachol‐induced [Ca2+]i oscillations by Ca2+ influx in single intestinal smooth muscle cells

Komori, Seiichi; Iwata, Masashi; Unno, Toshihiro; Ohashi, Hidenori

doi:10.1111/j.1476-5381.1996.tb15978.x

Cited by 18 publications

(18 citation statements)

References 38 publications

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“…Furthermore, in the presence of IP 3 receptor monoclonal antibodies or heparin in the patch pipette, muscarinic agonists did not induce any inward current, suggesting that IP 3 plays an important role in those smooth muscles (24,34). A different type of IP 3 -dependent oscillating inward currents has been reported in intestinal smooth muscle (20,37). This oscillating inward current is ascribed to nonselective cation channels, and Ca 2ϩ influx through voltage-sensitive Ca 2ϩ channels is involved in generating this oscillation.…”

Section: Discussionmentioning

confidence: 94%

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

Kajioka¹,

Nakayama²,

Asano³

et al. 2005

American Journal of Physiology-Cell Physiology

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The urinary bladder pressure during micturition consists of two components: an initial, phasic component and a subsequent, sustained component. To investigate the excitation mechanisms underlying the sustained pressure, we recorded from membranes of isolated detrusor cells from the pig, which can be used as a model for human micturition. Parasympathomimetic agents promptly evoke a large transient inward current, and subsequently during its continuous presence, oscillating inward currents of relatively small amplitudes are observed. The two types of inward current are considered to cause the phasic and sustained pressure rises, respectively. Ionic substitution and applications of channel blockers revealed that Ca(2+)-activated Cl(-) channels were responsible for the large transient and oscillating inward currents. Furthermore, the inclusion of guanosine 5'-O-(2-thiodiphosphate) in the patch pipette indicates that both inward currents involve G proteins. However, applications of heparin in the patch pipette and of xestospongin C in the bathing solution suggest a signaling pathway other than inositol 1,4,5-trisphosphate (IP(3)) operating in the inward current oscillations, unlike the initial transient inward current. This IP(3)-independent inward current oscillation system required both sustained Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular stores. These two requirements are presumably SKF-96365-sensitive cation channels and ryanodine receptors, respectively. Experiments with various Ca(2+) concentrations suggested that Ca(2+) influx from the extracellular space plays a major role in pacing the oscillatory rhythm. The fact that distinct mechanisms underlie the two types of inward current may help in development of clinical treatments of, for example, urinary incontinence and residual urine volume control.

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Section: Discussionmentioning

confidence: 94%

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

Kajioka¹,

Nakayama²,

Asano³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…Alternatively, they were bathed in a Cs + -rich solution consisting of 120 mM CsCl, 12 mM glucose, and 10 mM HEPES (pH adjusted to 7.4 with CsOH) and dialyzed with another Cs + -rich solution consisting of 80 mM CsCl, 1.0 mM MgATP, 1.0 mM Na 2 GTP, 5 mM creatine, 20 mM glucose, 10 mM HEPES, 10 mM BAPTA, and 4.6 mM CaCl 2 (calculated free-ionized calcium = approximately 100 nM; pH adjusted to 7.4 with CsOH; Cs + = 144 mM in total). Cell dialysis with the Cs + -rich solutions prevented generation of K + current by muscarinic agonists (17,18). The use of the latter pair of bathing and pipette solutions prevented mI cat modulation by changes in cytosolic Ca…”

Section: Current Recordingsmentioning

confidence: 99%

Characterization of Muscarinic Receptor-Mediated Cationic Currents in Longitudinal Smooth Muscle Cells of Mouse Small Intestine

et al. 2006

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Abstract. In mouse intestinal smooth muscle cells held at −50 mV, carbachol evoked an atropine-sensitive inward current in the intracellular presence of Cs + . The current response consisted of an initial peak followed by a smaller plateau component on which oscillatory currents frequently arose. Results from various experimental procedures indicated that the inward current is a muscarinic receptor-operated cationic current (mI cat ) sensitive to cytosolic Ca ] i buffered to 100 nM, the mI cat response to cumulative carbachol applications was inhibited competitively by an M 2 -selective antagonist but non-competitively by an M 3 -selective one. Also it was severely reduced by pertussis toxin (PTX) treatment or a phospholipase C (PLC) inhibitor. Comparative analysis of mI cat in mouse and guinea-pig intestinal myocytes indicated that the underlying channels resemble between those myocytes in agonist sensitivity, current-voltage relationship, and unitary conductance. The results suggest that in mouse intestinal myocytes, mI cat arises mainly via an M 2 / M 3 synergistic mechanism involving PTX-sensitive G-proteins and PLC activity in the absence of current modulation by [Ca 2+ ] i changes, as described for guinea-pig ileal mI cat . The channels underlying mI cat are also indistinguishable in gating properties between both types of myocytes.

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“…Unless otherwise stated, measurements of I cat were made usually in the extracellular presence of a Cs release from internal stores (20,21).…”

Section: Current Recordingsmentioning

confidence: 99%

Phospholipase C Involvement in Activation of the Muscarinic Receptor-Operated Cationic Current in Guinea Pig Ileal Smooth Muscle Cells

et al. 2004

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Abstract. In guinea pig single ileal smooth muscle cells held under voltage-clamp, the role of phospholipase C (PLC) in activation of the muscarinic receptor-operated cationic current (I cat ) was studied. U73122, a PLC inhibitor, prevented the generation of I cat by the muscarinic agonist carbachol. The effect did not involve muscarinic receptor block since it also blocked I cat which was evoked by GTPgS applied intracellularly to activate G proteins bypassing muscarinic receptors. Also, neither cationic channel block nor other possible nonspecific actions seemed to be involved since its analogue (U73343), structurally close but deficient of the PLC-inhibiting activity, did not significantly affect carbachol-or GTPgS-evoked I cat . Antibodies against the a subunits of G q / G 11 proteins (Ga q / Ga 11 -antibody) blocked only the small component of carbachol-evoked I cat , which was associated with an increase in [Ca 2+ ] i linked to an increase in G q/ 11 protein-regulated PLC activity. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG) produced via PLC-catalyzed metabolism, produced no or only a small current by itself, with the carbachol-evoked I cat remaining unchanged. These results provide evidence for the importance of PLC in I cat generation, and they also strongly suggest that the activity of PLC involved in the primary activation of I cat is neither under regulation by G q/ 11 proteins nor dependent on the action of DAG.

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Modulation of carbachol‐induced [Ca²⁺]_i oscillations by Ca²⁺ influx in single intestinal smooth muscle cells

Cited by 18 publications

References 38 publications

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

Characterization of Muscarinic Receptor-Mediated Cationic Currents in Longitudinal Smooth Muscle Cells of Mouse Small Intestine

Phospholipase C Involvement in Activation of the Muscarinic Receptor-Operated Cationic Current in Guinea Pig Ileal Smooth Muscle Cells

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