Nicotinic acetylcholine receptors in isolated type I cells of the neonatal rat carotid body.
Electrophysiological responses of enzymatically isolated type I cells from the neonatal rat carotid body to cholinergic agonists were examined using the whole-cell patch-clamp technique. Inward currents were evoked in cells clamped at -70 mV in response to bath-applied carbachol and two selective nicotinic agonists, nicotine and dimethylphenylpiperazinium. Muscarine failed to produce any change in membrane current. Responses to nicotine were concentration-dependent and also voltage-dependent, showing strong rectification positive to -40 mV. Currents evoked by nicotine were reduced or abolished in the presence of mecamylamine and also by high concentrations of atropine (10 or 100 microM). Under "current-clamp", nicotine was shown to depolarize type I cells, an effect which was only slowly reversible, but which could be rapidly attenuated by introduction of mecamylamine to the perfusate. In voltage-clamped cells, nicotine could evoke inward currents when extracellular Na+ was replaced by Ca2+. Our results demonstrate the presence of functional nicotinic acetylcholine receptors on type I cells of the neonatal rat carotid body. Activation of these receptors could lead to excitation of the intact carotid body by either of two possible mechanisms: depolarization of type I cells sufficient to open voltage-gated Ca2+ channels, or Ca2+ influx through the receptor pore itself. Either (or both) mechanisms could trigger catecholamine release from type I cells, which is a fundamental step in chemotransmission.
Department of Pharmacology, Leeds University, U.K.
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Wyatt
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Peers
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D002469:Cell Separation; D004594:Electrophysiology; D009538:Nicotine / Q000494:pharmacology; D009994:Osmolar Concentration; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*
D010277:Parasympathomimetics; D011978:Receptors, Nicotinic; D009538:Nicotine; D002118:Calcium