Biophysical Factors that Promote Mechanically-Induced Action Potentials in Neocortical and Hippocampal Pyramidal Neurons

Abstract

Pressure activation of single mechanosensitive (MS) cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons (Nikolaev et al., 2015). Here we describe several factors that underlie this powerful influence on neuronal activity. First, cell-attached patch recordings indicate the MS cation channels are located on the soma and therefore inject a depolarizing current close to the axonal initial segment/spike initiation zone (SIZ) where action potential threshold is lowest. Second, the rapid rise of the single MS channel current (< 50 µs) generates a rapid depolarizing (dV/dt) event that lowers spike threshold by favoring fast Na+ channel activation over slower inactivation. Finally, with pressure activation the gating of the MS channel switches from single brief spontaneous openings (< 1 ms) to longer bursts of openings (∼ 10 ms) during which a spike may be triggered by each stochastic opening within the burst. Thus, the combination of SIZ proximity and rapid, burst gating underlies the powerful influence of single MS channels on central neuronal activity. For comparison, whereas a unitary excitatory post-synaptic current activated on a distal dendrite typically fails to trigger an action potential even when generating as much as 1000 fC charge transfer across the synaptic membrane, a single MS channel current that generates less than 200 fC can trigger repetitive spiking.Nikolaev, Y.A. et al., Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons (2015) Brain Research. 1608: 1-13.