Voltage-gated Na+ channels in chemoreceptor afferent neurons—Potential roles and changes with development

Abstract

Carotid body chemoreceptors increase their action potential (AP) activity in response to a decrease in arterial oxygen tension and this response increases in the post-natal period. The initial transduction site is likely the glomus cell which responds to hypoxia with an increase in intracellular calcium and secretion of multiple neurotransmitters. Translation of this secretion to AP spiking levels is determined by the excitability of the afferent nerve terminals that is largely determined by the voltage-dependence of activation of Na+ channels. In this review, we examine the biophysical characteristics of Na+ channels present at the soma of chemoreceptor afferent neurons with the assumption that similar channels are present at nerve terminals. The voltage dependence of this current is consistent with a single Na+ channel isoform with activation around the resting potential and with about 60-70% of channels in the inactive state around the resting potential. Channel openings, due to transitions from inactive/open or closed/open states, may serve to amplify external depolarizing events or generate, by themselves, APs. Over the first two post-natal weeks, the Na+ channel activation voltage shifts to more negative potentials, thus enhancing the amplifying action of Na+ channels on depolarization events and increasing membrane noise generated by channel transitions. This may be a significant contributor to maturation of chemoreceptor activity in the post-natal period.

Pain transduction: a pharmacologic perspective

“…Sodium channels cycle through closed, open, and inactivated states [58]. Nav channels are composed of one alpha subunit and a variable number of beta subunits.…”

“…At resting membrane potential, Nav channels are found in a closed state, which prevents ion influx. With membrane depolarization, S4 voltage sensors cause movement of the activation gate, allowing extracellular sodium ions to enter through the alpha subunit [58]. The brief period of rapid ion influx causes a significant increase in membrane potential, eventually reaching the threshold required for action potential generation.…”

“…The brief period of rapid ion influx causes a significant increase in membrane potential, eventually reaching the threshold required for action potential generation. As the membrane potential becomes more positive a loop linking domains III and IV known as the “fast inactivation gate”, also positively charged, occludes the Nav channel and stops further ion influx [56, 58, 59]. During the period of inactivation, the Nav channels are largely refractory to further stimuli until the membrane is fully repolarized.…”

“…They found that systemic administration of the specific antagonist relieved pain six times better than lidocaine [75]. Because Nav 1.8 channels are concentrated in small peripheral nervous system nociceptive neurons and only sparsely present in other locations, a drug that targets Nav 1.8 specifically is likely to be free of many of the side effects incident to other sodium channel blocking drugs [56, 58]. …”

Study on the Complex Neuron Model’s Reduction and Its Dynamic Characteristics

“…Depending on electrophysiological experiments and new technologies such as optics imaging, some models of hippocampal pyramidal neuron based on ionic conductance have been successfully constructed [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The hippocampal CA1 pyramid neuron [11] generates frequent discharge actions.…”