The calcium dependence of tension development in depolarized smooth muscle

Durbin, Richard P.; Jenkinson, D. H.

doi:10.1113/jphysiol.1961.sp006707

Cited by 100 publications

(34 citation statements)

References 14 publications

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“…The most likely explanation is that the concentration of Ca2+ in the cytosol of the depolarized muscle cells is high enough, even in the absence of agonists, to activate the PK(Ca) mechanism, which is then susceptible to inhibition by the agents tested. A raised [Ca2+]i is in keeping with the observation that the depolarized muscle develops tension, provided that the bathing fluid contains Ca2+ (Durbin & Jenkinson, 1961 The second subsidiary observation was that the neuromuscular blockers and apamin increased the amplitude of the spontaneous activity of the rabbit duodenum as well as the contractile response of the taenia caeci to physalaemin. This, too, could be a consequence of blockade of a PK(Ca) mechanism which under normal circumstances, it can be supposed, becomes activated by the increase in [Ca2+]i that occurs both during spontaneous activity and in response to agonists such as physalaemin.…”

Section: Discussionmentioning

confidence: 54%

Neuromuscular blocking agents inhibit receptor‐mediated increases in the potassium permeability of intestinal smooth muscle

Gater

Haylett

Jenkinson

1985

British J Pharmacology

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1 The neuromuscular blocking agents tubocurarine, atracurium and pancuronium have been tested for their ability to inhibit receptor-mediated increases in the K+ permeability of intestinal smooth muscle. 2 All three agents, as well as the bee venom peptide apamin, reduced both the resting efflux of 86Rb and the increase in efflux caused by the application of either bradykinin (1 jM) or an a,-adrenoceptor agonist, amidephrine (20 giM), to depolarized strips of guinea-pig taenia caeci. This suggested that, like apamin, the neuromuscular blocking agents inhibit the Ca2+-dependent K' permeability (PK(Ca)) mechanism which in this tissue is activated by a variety of membrane receptors.3 The concentrations (IC50s) of atracurium, pancuronium and (+ )-tubocurarine which reduced the effect of amidephrine on 86Rb efflux by 50% were 12, 37 and 67 jM respectively. 4 Also in keeping with an ability to block PK(Ca), the neuromuscular blockers and apamin reduced the inhibition by amidephrine and bradykinin of physalaemin-mediated contractions of the taenia caeci.The IC50 values were 15, 31 and 120 jiM for atracurium, tubocurarine and pancuronium respectively, and 2.3 nM for apamin. 5 Each of the neuromuscular blockers, and apamin, increased the spontaneous contractions of the rabbit duodenum and blocked the inhibitory effect of amidephrine thereon.6 It is concluded that the PK(Ca) mechanism in the longitudinal smooth muscle of the intestine resembles that of hepatocytes and sympathetic ganglion cells in its susceptibility to inhibition by neuromuscular blocking agents, as well as by apamin.

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Section: Discussionmentioning

confidence: 54%

Neuromuscular blocking agents inhibit receptor‐mediated increases in the potassium permeability of intestinal smooth muscle

Gater

Haylett

Jenkinson

1985

British J Pharmacology

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“…Furthermore, contractures produced in isotonic K solution or by application of carbachol was depressed (Figs.7 to 10). Provided that carbachol induces an increase of Na-and Ca-permeability in causing depolarization and contraction (DURBIN and JENKINSON, 1961 ;BOLTON, 1972) and that the development of K contractures of the pregnant mouse myometrium and guinea pig ileal muscle depends on Ca-influx from outside, the above results may lead to the conclusion that in the presence of these ions, the increase in Na-as well as Ca-permeabilities were prevented. Although little was investigated in the present experiment about the membrane response of the ileal muscle of guinea pig, it might be presumed from the mechanical investigation that similar electrical events as in mouse myometrium underlay in that muscle.…”

Section: Discussionmentioning

confidence: 99%

Modification of the Mechanical Response of the Smooth Muscles of Pregnant Mouse Myometrium and Guinea Pig Ileum by Cadmium and Manganese Ions

Osa¹

1974

Jpn.J.Physiol

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Summary Effects of divalent cations on pregnant mouse myometrium and guinea pig ileum were investigated by recording electrical and mechanical activities. 1. Application of transition metal cations (Mn, Cd, Co, Ni, and Zn) inhibited the spontaneous activities of mouse myometrium. Except for Mn, treatment with these cations in a concentration of 1 mM and for 1-2 min caused an irreversible suppression of the mechanical response. 2. Myometrial membrane was hyperpolarized with 0.5 mM Cd decreasing membrane resistance. During application, contractures induced by excess K or carbachol was inhibited. After treatment with 0.5-1 mM Cd for 1-2 min, electrical and mechanical activities dissociated, i.e. spike activity resumed but mechanical activity was suppressed. The membrane was depolarized by carbachol to the control value, but contraction did not developed. 3. By contrast, contracture of mouse myometrium induced by excess K or carbachol application were potentiated after treatment with Mn. 4. The effects of divalent cations on guinea pig ileum were essentially the same as with mouse myometrium, i.e. treatment with Mn potentiated mechanical response whereas other ions caused irreversible suppression.In the mammalian myocardium, polyvalent cations such as Ni, Co, and Mn ions commonly depress Ca conductivity, while leaving the fast transient Na current only slightly affected (KAUFMANN and FLECKENSTEIN, 1965;OCHI, 1970;KOHLHARDT et al., 1973). This may lead to a decreased Ca influx into the depolarized myocardial cell so that decoupling of excitation-contraction mechanism occurs as in simple Ca-deficient media. A recent report on the rabbit atrium indicates that Cd induces a marked depression of the action potential. In addition, the contractile force-rate curve is significantly depressed by the ion (TODA,

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“…The intracellular calcium is maintained at a lower concentration than the extracellular calcium against an electrochemical gradient. Durbin & Jenkinson (1961) suggested that the carbachol contraction of depolarized smooth muscle is a consequence of the net movement of calcium into the muscle cells, following the increase in permeability produced by the drug. They noted the dependence of the 'maintained phase ' of the contraction on the concentration of calcium in the bathing fluid.…”

Section: Discussionmentioning

confidence: 99%

“…With a large dose of the agonist, however, the contraction may 'fade' at least temporarily from a rapidly attained peak. Fade has been observed in experiments with the ileum and taenia coli of the guinea-pig (Fastier & Reid, 1952;Paton, 1961;Durbin & Jenkinson, 1961;Ariens, Simonis & van Rossum, 1964). It has been obtained with isotonic recording, especially with heavy loading (Fastier & Reid, 1952;Ariens et al, 1964) and auxotonic recording (Paton, 1961).…”

Section: Introductionmentioning

confidence: 88%

Observations on ‘fade’: a complication of the contractile response of smooth muscle to a large dose of an agonist

Fastier

Purves

Taylor

1973

British J Pharmacology

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Summary1. A study has been made of the time course of contraction of guinea-pig isolated ileum when suddenly exposed to a high concentration of acetylcholine, carbachol or histamine. With a sufficiently large dose there was a 'fading' of the abrupt initial contraction. A sustained contraction followed, provided that the agonist was not washed out of the organ bath. 2. The fade produced by giving large equipotent doses of acetylcholine and histamine simultaneously was substantially greater than that obtained by giving either agonist alone. It was comparable to that produced by a double dose of acetylcholine or histamine. This result does not support any explanation of fade based on receptor occupancy. 3. The extent of fade and the level of the sustained contraction were strongly affected by the calcium concentration of the bath fluid: the higher the calcium concentration the less was the fade. It is suggested that fade occurs when there is such intense stimulation of receptors that excitation-contraction coupling becomes temporarily less efficient due to depletion of calcium from a store.

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The calcium dependence of tension development in depolarized smooth muscle

Cited by 100 publications

References 14 publications

Neuromuscular blocking agents inhibit receptor‐mediated increases in the potassium permeability of intestinal smooth muscle

Neuromuscular blocking agents inhibit receptor‐mediated increases in the potassium permeability of intestinal smooth muscle

Modification of the Mechanical Response of the Smooth Muscles of Pregnant Mouse Myometrium and Guinea Pig Ileum by Cadmium and Manganese Ions

Observations on ‘fade’: a complication of the contractile response of smooth muscle to a large dose of an agonist

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