Dr Morven Cameron, School of Medicine, Western Sydney University, NSW
Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In ‘conventional’ spiking neurons, it is the activation of voltage-gated sodium channels (NaV-channels) that leads to action potential generation. However, several other types of voltage-gated channels are expressed that also respond to electrical stimulation. In this study we examine the response of voltage-gated potassium channels (KV-channels) to brief electrical stimulation by whole-cell patch clamp electrophysiology and computational modelling. We show that non-spiking neurons of the retina exhibit a large variety of intrinsic responses to stimulation that are driven by several KV-channel subtypes. Computation modelling of this response reveals substantial differences in the response of specific KV-channels subtypes that is dependent on activation and inactivation kinetics. This suggests that the expression levels of different KV-channel subtypes in retinal neurons are a crucial predictor of the response that can be obtained. Furthermore, activation of KV-channels may antagonise currents driven by NaV-channels, and ultimately the probability of action potential generation. These data expand our knowledge of the mechanism of neuronal stimulation and suggest that KV-channel expression, which is variable in the central nervous system, is an important determinant of the sensitivity of neurons to electrical stimulation.