Cellular mechanisms of supersensitivity to acetylcholine and potassium ion after ciliary ganglionectomy in the rat iris sphincter muscle.

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The effect of parasympathectomy on the electrical and nonelectrical activation of iris smooth muscle cells was examined 7-10 days after ciliary ganglionectomy in order to explore the mechanisms involved in the nonspecific denervation supersensitivity. Resting membrane potential of rat iris sphincter muscle cells was not altered by cholinergic denervation. Although the degree of depolarization induced by raising [K]<SUB>o</SUB> was little affected by denervation, K-contracture was always potentiated. Acetylcholine (ACh) never modified membrane potential in normal iris muscles even at a high concentration of 50 μM. After denervation, ACh produced a much larger contraction, and at higher concentrations, concomitantly produced a depolarization which was far too small to account for the enhanced contraction. There were 3 and 4.6-fold increases in sensitivity to Ca and Sr, respectively, in the contractile response in high-K, Ca-free solution after denervation. The response to Ca was greatly enhanced also in height, and a large part of the increment of the response to 2 mM Ca was suppressed by 0.1 μM nifedipine. In the depolarized muscle of normal irides, Mn ion had two distinct effects, a calcium blocking effect at lower concentrations (≤1.2 mM) and a contractile effect at higher concentrations (≥1 .8 mM). Denervation caused a marked increase in the contractile effect of Mn (≥=0.6 mM). ACh elicited phasic contraction only once in the absence of external Ca. This response was much enhanced by parasympathectomy. Fluoride ion (F) also produced a distinct contraction many times in the Ca-free solution. F-induced contraction was much larger in denervated muscle than in normal muscle. These results i) indicate that denervation of the rat iris sphincter muscle does not significantly affect the electrical property of the muscle cells, ii) and suggest that denervation may increase Ca-influx of the cell membrane, iii) may increase the amount of releasable Ca from an intracellular store site, and iv) might increase the functional activity of the contractile protein.
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Cellular mechanisms of supersensitivity to acetylcholine and potassium ion after ciliary ganglionectomy in the rat iris sphincter muscle.

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