Modeling Excitability in Mechanosensory Neurons with MS Cation and MS Kv Channels

Abstract

In mechanosensory neurons, depolarizing receptor potentials arise from mechanosensitive (MS) cation channels (ECation=∼0 mV), but new findings in touch and pain neurons indicate that firing characteristics are precisely modulated by MS Kv channels. Depending on the context in which it is elicited, mechanically facilitated Kv1 activation puts the brakes on mechanosensory firing thresholds or frequencies (Hao et al 2013 Neuron 77:899). This can, for instance, ensure that only intense (noxious) mechanical stimuli generate action potential (AP) traffic in high-threshold neurons. Here we use AP modeling to explore qualitatively how Kv channel mechanosensitivity could affect threshold behaviors and AP frequency characteristics. An important unsettled question is which transition(s) in the Kv channel's activation path accounts for Kv mechanosensitivity. Mechanosensitivity could reside with a voltage dependent step or with the thermal opening transition (Tabarean & Morris 2002 Biophys J 82:2982; Schmidt et al 2012 PNAS 109:10352). During membrane deformations this mechanistic “detail” would be consequential, we argue, because the MS transition's location can powerfully affect the magnitude of gKmax(apparent) and deactivation time course rates. To allow us computational access to the specific Kv transitions, we run a hybrid HH/Markov AP model. While the standard excitability machinery is given in HH terms, the MS conductances are described in Markov fashion. To mimic the effect of a membrane stretch deformation on the MS gK, the forward/backward rates of either the concerted voltage-dependent closed-closed transition or the thermal open-closed transition are increased/decreased reciprocally (e.g., doubled/halved). Mechanoreceptor neurons can exhibit phasic responsiveness to sustained mechanical stimuli; to explore such behavior, terms are included that allow for the possibility that the two MS conductances, MS gCation and the MS gK, experience deformation onset/offset intensities differently. Supported by NSERC Canada & by OHRI.