Activation and desensitization of acetylcholine receptors in fish muscle with a photoisomerizable agonist.

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RESUMO

Voltage-clamped muscle fibres of the fish Xenomystus nigris were bathed in a solution containing 3,3-bis[alpha-(trimethylammonium)methyl]azobenzene (cis-Bis-Q; 100 nM). A flash of light photoisomerized some of the cis-Bis-Q (non-agonist form) to trans-Bis-Q (agonist form). This resulted in agonist-induced current. Current noise of channels activated by both trans-Bis-Q and ACh was analysed to find the channel conductances and open times associated with these two agonists. Channels activated by trans-Bis-Q and ACh had similar conductances (20-30 pS) and open times (3-4 msec) despite the photolabile azobenzene group of Bis-Q. Light flashes subsequent to the first flash caused further increases in the ratio of trans-Bis-Q to cis-Bis-Q and accompanying increases in agonist-induced current. Eventually, agonist-induced currents levelled off as a photo-equilibrium state was reached with a constant trans:cis ratio. After the photo-equilibrium current level was reached, light flashes caused temporary increases in agonist-induced current which decayed back to equilibrium in seconds. This result is interpreted according to a model in which trans-Bis-Q molecules are bound to a subpopulation of desensitized receptors, preventing recovery to native receptor. A flash of light then converts some trans-Bis-Q molecules bound to the desensitized receptor to the cis isomer. The newly formed cis-Bis-Q molecule may then unbind, allowing the desensitized receptor to recover. When light was flashed on muscle exposed to 300-600 nM-cis-Bis-Q, large (100-200 nA) agonist-induced currents were produced. These currents decayed exponentially over several seconds as the fibre desensitized. This result confirms that a first-order process underlies the onset of desensitization.

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