Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract

Abstract

The voltage-gated K(+) channel Kv1.3 has been reported to regulate transmitter release in select central and peripheral neurons. In this study, we evaluated its role at the synapse between visceral sensory afferents and secondary neurons in the nucleus of the solitary tract (NTS). We identified mRNA and protein for Kv1.3 in rat nodose ganglia using RT-PCR and Western blot analysis. In immunohistochemical experiments, anti-Kv1.3 immunoreactivity was very strong in internal organelles in the soma of nodose neurons with a weaker distribution near the plasma membrane. Anti-Kv1.3 was also identified in the axonal branches that project centrally, including their presynaptic terminals in the medial and commissural NTS. In current-clamp experiments, margatoxin (MgTx), a high-affinity blocker of Kv1.3, produced an increase in action potential duration in C-type but not A- or Ah-type neurons. To evaluate the role of Kv1.3 at the presynaptic terminal, we examined the effect of MgTx on tract evoked monosynaptic excitatory postsynaptic currents (EPSCs) in brain slices of the NTS. MgTx increased the amplitude of evoked EPSCs in a subset of neurons, with the major increase occurring during the first stimuli in a 20-Hz train. These data, together with the results from somal recordings, support the hypothesis that Kv1.3 regulates the duration of the action potential in the presynaptic terminal of C fibers, limiting transmitter release to the postsynaptic cell.

A C-terminal PDZ binding domain modulates the function and localization of Kv1.3 channels

“…The electrophysiological measurements indicate that the mutation did not affect voltage-dependence or the amount of functional channel in the plasma membrane. Previous studies [8, 10, 20] and the images in Fig. 1C indicate that a significant fraction of the channel is localized to an intracellular compartment which we have identified as the Golgi apparatus [8].…”

“…Kv1.3-deficient mice have altered body weight [4, 5] and Kv1.3 influences glucose transport in adipocytes and skeletal muscle [6, 7]. In neurons, Kv1.3 influences resting membrane potential, action potential characteristics, and neurotransmission [4, 8–10]. …”

Activation of 5-hyrdoxytryptamine 7 receptors within the rat nucleus tractus solitarii modulates synaptic properties

“…Only nTS cells connected to TS-afferents with a single synapse (i.e., monosynaptic) were included in this study. Recorded neurons were considered monosynaptic if the standard deviation of the latency time (“jitter”) was less than 300 μs over 30 events (Austgen et al, 2012; Ramirez-Navarro et al, 2011). Neurons in the present study were monosynaptic second-order as indicated by low jitter and latency.…”

The serotonin 5-HT2Creceptor and the non-addictive nature of classic hallucinogens

“…In addition, activation of Kv1.x inhibits cell-firing frequency and delays the onset of action potentials ( Lioudyno et al, 2013 ). Conversely, Kv1.x channel blockers prevent the flow of potassium ions, causing spontaneous depolarization and increasing, for example, action potential frequency and neurotransmitter release ( Ramirez-Navarro et al, 2011 ; Simeone et al, 2013 ; Tibbs et al, 1996 ). There are several excellent reviews on Kv channel localization in the brain, their trafficking, structure, and function, and involvement in brain disease pathophysiology ( D'Adamo et al, 2013 ; Heusser and Schwappach, 2005 ; Johnston et al, 2010 ; Robbins and Tempel, 2012 ; Robertson, 1997 ; Shah and Aizenman, 2014 ; Wang et al, 1994 ).…”