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

Abstract

Abstract-The effect of parasympathectomy on the electrical and nonelectrical activation of iris smooth muscle cells was examined 7-10 days after ciliary gan glionectomy in order to explore the mechanisms involved in the nonspecific dener vation supersensitivity. Resting membrane potential of rat iris sphincter muscle cells was not altered by cholinergic denervation. Although the degree of depolari zation induced by raising [K]o 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 iiM. 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 W 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 parasympa thectomy. 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.

Supersensitivity by AF64A, a Novel Inhibitor of Neuronal Choline-Uptake, of the Rat Iris Sphincter Smooth Muscle.

“…An increase in the sensitivity of the contractile proteins by a change in the activity or amount of calmodulin has been proposed to explain the supersensitivity induced by the sympathetic denervation (Ramos et al, 1986). Similar possibility has been suggested in parasympathectomized iris sphincter or dilator (Hasegawa et al, 1987Banno et al, 1987Hashimoto et al, 1993. Further experiments are required , especially using skinning tech niques, to elucidate the mechanisms for AF64A-induced nonspecific supersensitivity.…”

“…Since most of parasympathetic ganglia are located in the target organs, the surgical denervation is not practical except for a few organs. Surgical parasympathetic denervation of iris smooth muscle can be performed by ciliary ganglionectomy and results in solution), respectively, in the sphincter (Hasegawa et al, 1987 ;Banno et al, 1987) or the dilator (Hasegawa et al, 1988 ;Hashimoto et al, 1993). The chemical sympathetic denervation using 6-hydroxydopamine (Kostrzewa and Jacobowitz, 1975) or guanethidine (Burnstock et al, 1971 ;Shibata et al, 1989) and the depletion of noradrenaline in sympathetic nerve endings using reserpine (Trendelenburg and Gravenstein, 1958 ;Zaimis, 1961) have been giving advantages to clarify neuronal controls of tissue functions by both central and peripheral sympathetic nerves.…”

Parasympathetic denervation supersensitivity in the rat iris sphincter muscle : An in vitro study.

“…The sensitivity was increased not only to transmitter (ACh) but to another unrelated drug (5-HT). A particularly critical aspect of this nonspecificity is an increase in maximum response to ions such as potassium (cat nictitating membrane (25); rabbit aorta (26)) and calcium (27)(28)(29).…”

Pertussis toxin‐sensitive muscarinic relaxation in the rat iris dilator muscle

“…After ciliary ganglionectomy, there is increased responsiveness to a variety of agonists in both rat iris sphincter and dilator muscles. The mechanism of nonspecific supersensitivity remains unclear (Banno et al, 1987;Hasegawa et al, 1987;1988;Hashimoto et al, 1993). Although it is possible that blockade of muscarinic relaxation after parasympathectomy is due to changes in G protein, this possibility was not examined directly in the present study.…”