Two distinct classes of functional 7-containing nicotinic receptor on rat superior cervical ganglion neurons.
Nicotinic acetylcholine receptors (nAChRs) that bind alpha-bungarotoxin (alpha Bgt) were studied on isolated rat superior cervical ganglion (SCG) neurons using whole-cell patch clamp recording techniques. Rapid application of ACh onto the soma of voltage clamped neurons evoked a slowly desensitizing current that was reversibly blocked by alpha Bgt (50 nM). The toxin-sensitive current constituted on average about half of the peak whole-cell response evoked by ACh. Nanomolar concentrations of methyllycaconitine blocked the alpha Bgt-sensitive component of the ACh-evoked current as did intracellular dialysis with an anti-alpha 7 monoclonal antibody. The results indicate that the slowly reversible toxin-sensitive response elicited by ACh arises from activation of an unusual class of alpha 7-containing receptor (alpha 7-nAChR) similar to that reported previously for rat intracardiac ganglion neurons. A second class of functional alpha 7-nAChR was identified on some SCG neurons by using rapid application of choline to elicit responses. In these cases a biphasic response was obtained, which included a rapidly desensitizing component that was blocked by alpha Bgt in a pseudo-irreversible manner. The pharmacology and kinetics of the responses resembled those previously attributed to alpha 7-nAChRs in a number of other neuronal cell types. Experiments measuring the dissociation rate of 125I-labelled alpha Bgt from SCG neurons revealed two classes of toxin-binding site. The times for toxin dissociation were consistent with those required to reverse blockade of the two kinds of alpha Bgt-sensitive response. These results indicate that rat SCG neurons express two types of functional alpha 7-nAChR, differing in pharmacology, desensitization and reversibility of alpha Bgt blockade.
Cuevas
J
J
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, FL 33612-4799, USA.
Roth
A L
AL
Berg
D K
DK
D000109:Acetylcholine / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry* / Q000502:physiology*; D018697:Nootropic Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011978:Receptors, Nicotinic / Q000145:classification* / Q000235:genetics / Q000276:immunology; D017783:Superior Cervical Ganglion / Q000166:cytology*; D014665:Vasodilator Agents / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D007306:Insecticides; D007457:Iodine Radioisotopes; D018697:Nootropic Agents; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014665:Vasodilator Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D002794:Choline; D000109:Acetylcholine; D000157:Aconitine