K channels as ROS-dependent modulator of neurotransmitter release at the neuromuscular junctions.

AIMS

Neurotransmitter release requires high energy demands, making the nerve terminals metabolically fragile and susceptible to oxidative stress. ATP-sensitive potassium (K) channels can be an important regulator orchestrating the influence of metabolic-related signals on exocytosis. Here, the relevance of ROS in K channel-dependent control of neurotransmitter release at the frog neuromuscular junction was studied.

METHODS

Microelectrode recordings of end plate potentials at the distal and proximal compartments of nerve terminals as well as fluorescent techniques were used.

KEY FINDINGS

Activation of K channels in the proximal region suppressed evoked and spontaneous release in a lipid raft-dependent manner. Activation of K channels in the distal region reduced solely evoked release which was preserved after lipid raft disruption. Chelation of ROS potentiated the effects of K channel activation and unmasked the effects of K channel blocker on evoked exocytosis. Activation or inhibition of K channels suppressed or enhanced the depressant action of extracellular adenosine on evoked exocytosis. This was accompanied with an increase or decrease in adenosine-induced ROS production, respectively. K channel-dependent modulation of adenosine action was halted by antioxidant and NADPH-oxidase inhibitor. Also, activation of K channels led to an increase in ROS production suppressing the negative effects of extracellular ATP on evoked release in a ROS-dependent manner.

SIGNIFICANCE

K channel-mediated modulation of release has specific features in distal and proximal compartments and depends on endogenous ROS levels and lipid raft integrity. Activation of K channels suppresses the action of extracellular adenosine and ATP on evoked release by increasing ROS production.