Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.

Sims, SM; Singer, Joshua J.; Walsh, Jr Jv

doi:10.1113/jphysiol.1985.sp015837

Cited by 100 publications

(52 citation statements)

References 47 publications

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“…While in some cells this depolarization may occur via activation of either a Na ÷ permeability or a non-selective cation permeability [30,31], in other cells it may result instead from a decrease in K ÷ permeability [29][30][31][32][33]. Several K ÷ channels in the plasma membrane of the pancreatic B-cell have been proposed to play a key role in both the regulation of membrane potential and in the modulation of electrical activity [34].…”

Section: Discussionmentioning

confidence: 99%

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Santos

Rojas

1989

FEBS Letters

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Acetyicholine (1-10/zM) depolarized the membrane and stimulated glucose-induced bursts of electrical activity in mouse pancreatic B-cells. The acetylcholine effects were mimicked by muscarine while nicotine had no effect on membrane potential. Pirenzepine, an antagonist of the classical M l-type muscarinic receptors, but not gallamine (1-100 gM), an antagonist of the classical M2-type receptors, antagonized the acetylcholine action on glucose-induced electrical activity (ICs0 =0.25/zM). Bethanechol, an agonist of the classical M2-type musearinic receptors, was approximately 100 times less effective than acetylcholine in stimulating the electrical activity. In addition, acetylcholine (1/~M) induced a marked increase (25%) in input resistance to the B-cell membrane. The results indicate that acetylcholine exerted its effects on the B-cell membrane by inhibiting K + conductance via activation ofa musearinic receptor subtype distinct from the classical M2-type receptor.

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Section: Discussionmentioning

confidence: 99%

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Santos

Rojas

1989

FEBS Letters

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“…carinic action on these smooth muscle cells is suppression of K+ current (2). This current bears a general similarity to the muscarine-sensitive K+ current, designated M-current, which was first described in sympathetic neurons (10)(11)(12).…”

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confidence: 91%

“…Single smooth muscle cells from the stomach of the toad B. marinus were dissociated by using an enzymatic digestion procedure (19)(20)(21) and were used within 24 hr of isolation. Cells prepared in this way have been shown to be viable by a number of criteria (4,6), including the ability to generate Ca2l action potentials (5) and to respond to a variety of agents that cause or block contraction (2,21).…”

Section: Methodsmentioning

confidence: 99%

Acetylcholine increases voltage-activated Ca2+ current in freshly dissociated smooth muscle cells.

Vivaudou¹,

Walsh²,

Singer³

1987

Proc. Natl. Acad. Sci. U.S.A.

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The regulation of voltage-activated Ca2+ current by acetylcholine was studied in single freshly dissociated smooth muscle cells from the stomach of the toad Bufo marinus by using the tight-seal whole-cell recording technique. Ca2+ currents were elicited by positive-going command pulses from a holding level near -80 mV in the presence of internal Cs' to block outward KV currents. Ca2+ current was greatest in magnitude at command potentials near 10 mV. At such command potentials, acetylcholine increased the magnitude of the inward current and slowed its decay. The effects of acetylcholine were seen in the absence of external Na' or with low Cl (aspartate replacement) in the bathing solution and could be mimicked by muscarine. The peak of the current-voltage relationship for the Ca2+ current was not discernibly shifted along the voltage axis by acetylcholine. These results demonstrate that activation of muscarinic receptors not only Acetylcholine, acting directly on muscarinic receptors in the smooth muscle cell membrane, causes depolarization, action potential generation, and, ultimately, contraction in a wide variety of smooth muscle types (1). To investigate the mechanism of acetylcholine action, we have used a preparation of freshly dissociated smooth muscle cells from the stomach of the toad Bufo marinus, where acetylcholine has been shown to exert an excitatory action (2-4). These cells have the advantage that their electrical activity has been extensively characterized by current-clamp (5, 6), voltageclamp (7,8), and patch-clamp (9) techniques.Recently, we demonstrated that one mechanism of muscarinic action on these smooth muscle cells is suppression of K+ current (2). This current bears a general similarity to the muscarine-sensitive K+ current, designated M-current, which was first described in sympathetic neurons (10)(11)(12) Series resistance compensation proved to be unnecessary since it was calculated that maximum inward currents produced a 2-to 5-mV error due to the series resistance and that the increase in current induced by acetylcholine or muscarine produced a 0.5-to 2-mV error. In what is referred to below as the standard voltage-clamp paradigm, the membrane potential was held at -78 mV for 6 sec, with alternating 3-sec command pulses to -98 and +9 mV, providing a total recovery time of 15 sec for the inward current. Deviations from this paradigm are indicated.Current and voltage signals were stored using an FM tape recorder, digitized later at a rate of 1 kHz after filtering (8-pole Bessel filter, 300-Hz cut-off) and analyzed with a PDP-11/73 computer system (Indec Systems). Traces shown in the figures were further filtered by using a digital gaussian filter (23), and in these cases the filter cut-off and effective sampling frequency are specified in the figure legends. Capacitive transients were blanked for reasons of clarity. Subtraction of the capacitive transients and leakage current with scaled averages of small (10-20 mV) hyperpolarizing pulses demonstrated that the inward curren...

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“…In portal vein smooth muscle, it is known that a1-adrenoceptor activation leads to the induction of three major currents, i.e. Ca2+-dependent K+ and Cl-currents and a small sustained cationic current (Byrne & Large, 1988; Pacaud, Loirand, Mironneau & Mironneau, 1989; Amedee, Benham, Bolton, Byrne & Large, 1990 a; Amedee, Large & Wang, 1990b;Wang & Large, 1991), although there is an exception in which noradrenaline is found to decrease a K+ conductance in the guinea-pig mesenteric vein (Suzuki, 1981) similar to muscarinic suppression of K+ conductance observed in bullfrog stomach (Sims, Singer & Walsh, 1985) or guinea-pig stomach (Lammel, Deitmer & Noack, 1991). The Ca2+-dependent K+ and Cl-currents are thought to be activated in response to an elevation of the intracellular Ca2" concentration ([Ca2+]i) which probably results from the inositol 1,4,5-trisphosphate-triggered Ca2+ release from the 428 C>ATIONA=-SrELECTIVE CHANNEL IN PORTAL VEIN4 sarcoplasmic reticulum (SR).…”

Section: Introductionmentioning

confidence: 99%

Dual regulation of cation‐selective channels by muscarinic and alpha 1‐adrenergic receptors in the rabbit portal vein.

Inoue

Kuriyama

1993

The Journal of Physiology

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SUMMARY1. The excitatory actions of phenylephrine (Phe) and acetylcholine (ACh) on the smooth muscle of rabbit portal vein were investigated and compared by using wholecell and single channel configurations of the patch clamp technique, in combination with a modified concentration jump method.2. At negative holding potentials with KCl (0-1 mm EGTA) electrodes, rapid applications of Phe (> 1 JtM) and ACh (> 10 /tM) both resulted in biphasic responses consisting of fast outward or inward currents and a long-lasting inward current with an increased noise level. 3. The slow inward current was still recorded when the cell was dialysed with caesium aspartate solution complemented with 10 mm EGTA, in order to eliminate contributions of calcium-dependent conductances (K+ and Cl-currents). Phe was more potent at activating the current than ACh. Ion replacement experiments revealed that both the Phe-and ACh-induced slow inward currents are cationselective conductances (CS currents).4. The I-V relationships of the Phe-or ACh-induced CS currents were similar both for the instantaneous peak and the steady state. The tail current analysis over a wide range of membrane potentials (-150 to + 100 mV) showed that depolarizations to very positive potentials (>+ 50 mV) from near the resting membrane potential (-40 mV) can produce a several-fold increase in the steady-state activation of the CS currents, but the maximal activations were in most cases not observed even at + 100 mV. 44 ims, respectively). In addition, the relative open probability (P.,rel) was no more than 0 2 in the voltage range of -100 to -30 mV for both 50 Jm Phe and 500 ,UM ACh, suggesting low open probabilities of the Phe-and ACh-activated CS channels near the resting membrane potential.7. The activation of the CS current by 100,am Phe was completely inhibited by application of 10 UM prazosin but not affected by that of aUM atropine, while the opposite results were observed for the CS currents activated by 100 /M ACh.8. From these results, we concluded that both the ax-adrenergic and muscarinic receptor regulate a common CS channel, and this may in part be responsible for the excitatory cholinergic and adrenergic actions in the rabbit portal vein.

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Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.

Cited by 100 publications

References 47 publications

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Acetylcholine increases voltage-activated Ca2+ current in freshly dissociated smooth muscle cells.

Dual regulation of cation‐selective channels by muscarinic and alpha 1‐adrenergic receptors in the rabbit portal vein.

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