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INTRACELLULAR OBSERVATIONS ON THE EFFECTS OF MUSCARINIC AGONISTS ON RAT SYMPATHETIC NEURONES
Author(s) -
BROWN D.A.,
CONSTANTI A.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb09778.x
Subject(s) - muscarine , muscarinic acetylcholine receptor , chemistry , depolarization , membrane potential , biophysics , tetraethylammonium , resting potential , conductance , rheobase , orthodromic , oxotremorine , acetylcholine , endocrinology , electrophysiology , medicine , biochemistry , biology , receptor , potassium , mathematics , organic chemistry , combinatorics
1 Responses of single neurones in isolated superior cervical ganglia of the rat to muscarinic agonists were recorded with intracellular microelectrodes. 2 (±)‐Muscarine (1 to 10 μ m ) and methylfurmethide (1 to 3 μ m ) produced reversible membrane depolarizations (≤ 15 mV) accompanied by a fall in input conductance and an increased tendency toward repetitive spike discharges. The spike configuration was unchanged. 3 Analysis of steady‐state current/voltage curves revealed the most consistent muscarinic effect to be a large reduction (∼50% at 10 μ m muscarine) in input slope conductance around rest potential. This conductance decrease diminished as the membrane was hyperpolarized, and the normal increase in slope conductance with membrane depolarization was depressed. The current/voltage curves in the presence and absence of agonist did not usually intersect; in a few tests, the curves intersected at between −65 and −88 mV (i.e. 9 to 28 mV hyperpolarized to rest potential). 4 Divalent cations (10 m m [Ca 2+ ] or [Mg 2+ ]) showed a small muscarine‐like effect on the current/voltage and slope conductance/voltage curves, but did not affect the action of muscarine itself. 5 Tetraethylammonium (TEA, 5 m m ) also had a small muscarine‐like effect, and depressed or reversed the action of muscarine. However, TEA differed from muscarine in blocking orthodromic transmission and prolonging direct spike repolarization. 6 It is concluded that the primary effect of muscarinic agonists is to alter the rectifying properties of the cell within the potential range −80 to −40 mV.