INTRACELLULAR OBSERVATIONS ON THE EFFECTS OF MUSCARINIC AGONISTS ON RAT SYMPATHETIC NEURONES

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Abstract
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 μm) and methylfurmethide (1 to 3 μm) 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 μm 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 mm [Ca2+] or [Mg2+]) 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 mm) 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.