Axonal membrane stretch suppresses neuronal excitability by activating mechanosensitive K2P channels at the node of Ranvier

Saltatory conduction is the propagation of action potentials along myelinated nerves, which enables fast propagation through the node of Ranvier. Recently, we demonstrated that K2P channels, TWIK-related K+ channel-1 (TREK-1), and TWIK-related arachidonic acid-activated K + channel (TRAAK), are highly expressed in the mammalian node of Ranvier of sensory nerves and have an important role in action potential repolarization instead of voltage-gated K+ channels. TREK-1/TRAAK channels are activated by membrane depolarization as well as various stimuli, such as temperature, pH, arachidonic acid, and mechanical membrane stretch. Although membrane mechanical stretch has been suggested to modulate action potential conduction, how membrane stretching modulates intrinsic electrophysiological properties at the node of Ranvier remains unclear. In the present study, we examined the effects of membrane stretch on neuronal membranes at the node of Ranvier in rat sciatic nerves. The single-channel conductance was approximately 90 pS at 80 mV. Membrane stretch increased the single-channel event numbers and open probability in a pressure-dependent manner. Consistent with single-channel activity, intra-pipette positive pressure increased outward leak currents and decreased membrane excitability in a whole-cell configuration. Furthermore, blockage of TREK-1/TRAAK channels by Ba2+ reversed the changes in the intrinsic electrophysiological properties induced by intra-pipette pressure. These results indicate that the activation of mechanosensitive TREK-1/TRAAK channels may suppress neuronal excitability following axonal stretch. Our findings suggest that TREK-1/TRAAK channels may play an important role in the prevention of ectopic action potential discharge at the axon by intense mechanical nerve stretch under physiological conditions.

Automated summary

Saltatory conduction allows fast propagation of action potentials along myelinated nerves by utilizing the node of Ranvier. The K2P channels TREK-1 and TRAAK were found to be highly expressed in the node of Ranvier and play a crucial role in action potential repolarization. In this study, membrane stretch was shown to increase single-channel event numbers and open probability, as well as decrease membrane excitability. Blockage of TREK-1/TRAAK channels reversed these changes, suggesting their activation suppresses neuronal excitability following axonal stretch. These findings indicate that TREK-1/TRAAK channels may prevent ectopic action potential discharge during intense mechanical nerve stretch.