On the neurotrophic control of acetylcholine receptors at frog end‐plates reinnervated by the vagus nerve.

Abstract

SUMMARY1. To test whether the properties of subsynaptic acetylcholine (ACh) receptors in skeletal muscle fibre are influenced by the type of the innervating neurone some pharmacological properties of ACh receptor in normal end-plates and in denervated end-plates reinnervated by the vagus nerve in the frog were compared.2. Blockade of nerve-evoked synaptic currents by 200 /M-hexamethonium was stronger at vagus-reinnervated than at normal end-plates. Blockade at both types of junctions was voltage dependent. The effect of hexamethonium on equilibrium currents induced by bath-applied ACh and carbamylcholine was similar at the two types of junctions. 3. At both normal and vagus-reinnervated junctions, decamethonium had similar partial agonist properties.4. Following a step in membrane potential, the relaxations of ACh-induced conductance changes at the two types of junctions were affected in a similar fashion by heximethonium: hyperpolarization first produced a fast decrease and then a slow exponential increase in conductance. Upon depolarization, a fast increase was followed by an exponential decline to its original level. The time constant of the slow relaxation was slightly prolonged compared to control. These findings are consistent with a fast blocking action of open channels by hexamethonium.5. The effectiveness of hexamethonium in blocking end-plate currents was reduced in the presence of (+ )-tubocurarine, indicating that hexamethonium has a competitive blocking action on the receptors.6. These results do not indicate that the pharmacological properties of the ACh receptors are changed after an end-plate is reinnervated by a preganglionic neurone. The differential effect of hexamethonium on transmission at normal and vagusreinnervated end-plates is discussed as a consequence of different transmitter release characteristics at the two types of junctions.

Modes of hexamethonium action on acetylcholine receptor channels in frog skeletal muscle

“…At + 50 mV, the concentration of hexamethonium required to reduce the agonist-induced current to approximately 50% was 200pM: this may be compared with the dissociation constant of hexamethonium binding to acetylcholine receptors measured from the rate of inhibition of abungarotoxin binding to receptors in denervated rat muscle, which is approximately 100pM (Colquhoun & Rang, 1976). Brenner & Micheroli (1985) also concluded that the action of hexamethonium at the frog endplate was in part a competitive block of receptors, combined with an action at ion channels which was not a simple sequential block.…”

“…Milne & Byrne (1981) investigated the effects of hexamethonium on endplate currents in frog muscle in which neuromuscular transmission had been blocked with high concentrations of magnesium and concluded that hexamethonium blocked open ion channels. More recently, Brenner & Micheroli (1985) concluded from a study on normal and vagus-reinnervated frog endplates that hexamethonium acted both as a competitive antagonist and as a channel blocking agent, although direct evidence for channel block could not be demonstrated.…”