Electrophysiological effects of norepinephrine on Purkinje neurons in intraocular cerebellar grafts: alpha- vs beta-specificity.
The present study investigates the receptor specificity of the electrophysiological effects of norepinephrine (NE) on cerebellar Purkinje neurons. Intraocular cerebellar grafts were utilized to allow both superfusion and local administration of selective adrenergic agonists and antagonists. Fetal cerebellar anlagen (E13-15) were homologously transplanted to the anterior chamber of the eye of adult recipient rats and allowed to mature in the eye for at least 5 weeks. Spontaneous activity of Purkinje neurons was recorded extracellularly in the intraocular grafts. Superfusion of 5 microM NE caused elevations of the spontaneous firing rate. Superfusion of 30 microM NE caused depressions, which were occasionally preceded by an excitation. Iontophoretic application of NE to grafted Purkinje neurons primarily caused depressions of the spontaneous discharge rate. Thus, the NE-induced excitations previously reported from in vitro slices are not anomalies of the in vitro slice preparation, but can be observed with superfusion of NE in our in vivo preparation as well. In general, the excitations caused by low doses of superfused NE were blocked by timolol, a specific beta-adrenergic antagonist, while the depressions caused by 30 microM superfused NE or iontophoretically applied NE were blocked by the specific alpha-adrenergic antagonist phentolamine. Large doses of sotalol were found to block both excitatory and depressant responses while lower doses only antagonized the NE-induced excitations. Taken together, these results suggest that the inhibitory effects of NE on PUrkinje neuron firing rate in intraocular cerebellar grafts in vivo are mediated via an alpha-adrenergic receptor mechanism, while the excitations caused by NE may be beta-mediated.
Granholm
A C
AC
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Palmer
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002531:Cerebellum / Q000196:embryology / Q000502:physiology / Q000637:transplantation*; D009638:Norepinephrine / Q000494:pharmacology*; D009799:Ocular Physiological Phenomena; D010646:Phentolamine / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D013999:Timolol / Q000494:pharmacology
D011941:Receptors, Adrenergic; D013999:Timolol; D009638:Norepinephrine; D010646:Phentolamine