Dissociation of contraction and potassium efflux in smooth muscle

1960 ◽  
Vol 199 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Leon Hurwitz ◽  
Betty Tinsley ◽  
Frank Battle

Normally, a pilocarpine induced contraction of the isolated guinea pig ileum is associated with a change in potassium transport across cell membranes. Bathing the tissue in a Ca-free medium will effect a dissociation between the contractile response and the potassium efflux. The replacement of Tyrode's solution by a Ca-free medium elicits a slight increase in smooth muscle tone followed by a return to a state of relaxation. Within an hour the contractile response to pilocarpine becomes negligible. This lack of response to pilocarpine applies to circular as well as longitudinal smooth muscle. In contrast to the changes which occur in muscle tone the efflux of potassium, following withdrawal of Ca ion, undergoes a sudden rise and remains above normal. The administration of pilocarpine, after the tissue has been bathed in the Ca-free medium for 1 or 2 hours, will still evoke a moderate additional increase in potassium efflux. Replacement of Ca ion with an equimolar quantity of Mg ion causes the contractile response to pilocarpine to disappear sooner than it would have in a simple calcium-free medium. Here, too, the potassium efflux of the tissue rises and after 1 hour responds to pilocarpine with a further increase. Thus, pilocarpine can modify potassium transport in the isolated ileum regardless of its effect on smooth muscle tone.

1961 ◽  
Vol 200 (4) ◽  
pp. 789-793 ◽  
Author(s):  
George B. Weiss ◽  
Robert E. Coalson ◽  
Leon Hurwitz

The longitudinal smooth muscle layer of the guinea pig ileum was isolated in order to investigate its contractile responses and unidirectional K42 fluxes. Pilocarpine (7.5 x 10–6 m), acetylcholine (6.6 x 10–6 m), and a modified Tyrode's solution in which potassium ion was substituted for almost all the sodium ion were employed as excitatory agents. Cocaine (8.5 x 10–4 m) and a calcium-free Tyrode's solution served as inhibitory agents. Smooth muscle tone and potassium efflux of this relatively pure tissue were both increased by all three excitatory substances. Moreover, acetylcholine and pilocarpine produced a decrease in the influx of potassium ion. Bathing the tissue in a calcium-free medium for 1 hour before introducing pilocarpine to the muscle bath eliminated the contractile response that this drug ordinarily produces, but did not diminish appreciably the increase in K42 efflux. These observations are qualitatively similar to results previously obtained in analogous experiments on isolated whole ileum. In addition, cocaine (8.5 x 10–4 m) was found to block the contractile response and about three-quarters of the enhanced K42 efflux elicited by the isotonic potassium solution. It is presumed that cocaine acting at the membrane impedes ion fluxes important for smooth muscle contraction.


1994 ◽  
Vol 72 (8) ◽  
pp. 919-936 ◽  
Author(s):  
Michael P. Walsh

Vascular smooth muscle tone is regulated primarily by the sarcoplasmic free Ca2+ concentration, which determines the level of myosin phosphorylation. Stimulation of the muscle results in an increase in free [Ca2+], whereupon Ca2+ binds to calmodulin, inducing a conformational change enabling calmodulin to interact with and activate myosin light chain kinase. The active Ca2+∙calmodulin∙myosin light chain kinase complex catalyses the phosphorylation of serine-19 of the two 20-kDa light chains of myosin; this triggers cross-bridge cycling and the development of force. Relaxation follows restoration of free [Ca2+] to the resting level, whereupon calmodulin dissociates from myosin light chain kinase, which is thereby inactivated, and myosin is dephosphorylated by myosin light chain phosphatase and remains detached from actin. Overwhelming evidence now exists in favour of the central role of myosin phosphorylation–dephosphorylation in smooth muscle contraction–relaxation. However, considerable evidence supports the existence of additional, secondary mechanisms that can modulate the contractile state of smooth muscle either by altering the Ca2+ sensitivity of the contractile response or otherwise modulating one of the molecular events occurring downstream of the Ca2+ signal, e.g., the interaction of phosphorylated myosin heads with actin. The interplay of several regulatory elements confers on the contractile response of vascular smooth muscle the high degree of flexibility and adaptability required for the effective regulation of blood pressure.Key words: calcium, myosin, protein kinases, protein phosphatases, signal transduction, regulation of contraction, caldesmon, calponin.


1963 ◽  
Vol 47 (1) ◽  
pp. 173-187 ◽  
Author(s):  
George B. Weiss ◽  
Leon Hurwitz

Inherent smooth muscle tone and acetylcholine-induced contractions of the isolated longitudinal muscle from guinea pig ileum are inhibited by 1.2 M ethanol. The inhibitions are antagonized by high concentrations of calcium ion in the external medium. Previous work has indicated that an acetylcholine-induced increase in potassium efflux from the ileal muscle is also inhibited by ethanol and reactivated by high concentrations of calcium ion. It was found in this study that, in addition to ethanol, a drastic reduction in the calcium ion concentration of the bathing medium appeared to produce a depression of this drug-induced increase in potassium efflux. Preincubating the muscle in a reduced calcium ion concentration also inhibited the increase in potassium efflux initiated by a high potassium medium. Conversely, the exposure of the muscle to 1.2 M ethanol did not depress the potassium-induced increase in potassium efflux. Increases in smooth muscle tone produced by a high potassium medium have been reported to be inhibited both by ethanol and by a depletion of external calcium. These data suggest that the calcium ions which activate or enhance a potassium-induced increase in potassium efflux are not bound to the same loci in the muscle fiber as those involved in an acetylcholine-induced increase in potassium efflux or those involved in a potassium-induced increase in smooth muscle tone.


CHEST Journal ◽  
1982 ◽  
Vol 81 (3) ◽  
pp. 396
Author(s):  
Elisabeth McIntyre ◽  
John H. Alpers ◽  
Richard E. Ruffin

2003 ◽  
Vol 551 (3) ◽  
pp. 955-969 ◽  
Author(s):  
T. K Smith ◽  
G. R Oliver ◽  
G. W Hennig ◽  
D. M O'Shea ◽  
P. V. Berghe ◽  
...  

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