Kv4 channels underlie A-currents with highly variable inactivation time courses but homogeneous other gating properties in the nucleus tractus solitarii

Abstract

In the nucleus of the tractus solitarii (NTS), a large proportion of neurones express transient A-type potassium currents (I KA) having deep influence on the fidelity of the synaptic transmission of the visceral primary afferent inputs to second-order neurones. Up to now, the strong impact of I KA within the NTS was considered to result exclusively from its variation in amplitude, and its molecular correlate(s) remained unknown. In order to identify which Kv channels underlie I KA in NTS neurones, the gating properties and the pharmacology of this current were determined using whole cell patch clamp recordings in slices. Complementary information was brought by immunohistochemistry. Strikingly, two neurone subpopulations characterized by fast or slow inactivation time courses (respectively about 50 and 200 ms) were discriminated. Both characteristics matched those of the Kv4 channel subfamily. The other gating properties, also matching the Kv4 channel ones, were homogeneous through the NTS. The activation and inactivation occurred at membrane potentials around the threshold for generating action potentials, and the time course of recovery from inactivation was rapid. Pharmacologically, I KA in NTS neurones was found to be resistant to tetraethylammonium (TEA), sea anemone toxin blood-depressing substance (BDS) and dendrotoxin (DTX), whereas Androctonus mauretanicus mauretanicus toxin 3 (AmmTX3), a scorpion toxin of the α-KTX 15 family that has been shown to block all the members of the Kv4 family, inhibited 80 % of I KA irrespectively of its inactivation time course. Finally, immunohistochemistry data suggested that, among the Kv4 channel subfamily, Kv4.3 is the prevalent subunit expressed in the NTS.

Effects of high-fat diet and gastric bypass on neurons in the caudal solitary nucleus

“…voltage dependency of activation, requirement of an initial hyperpolarization to deinactivate the channel, and a rapid inactivation (Cai, Li et al 2007; Johnston, Forsythe et al 2010; Gu and Barry 2011). Definitive identification of I A requires ion substitution to rule out the contributions of non K+ ions and a pharmacological sensitivity to 4-AP or other more specific K+ channel antagonists (Cai, Li et al 2007; Johnston, Forsythe et al 2010; Strube, Saliba et al 2015; Tsantoulas and McMahon 2014…”

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations

“…A computational model of a VTA dopamine neuron was created in Genesis simulation software (Bower and Beeman, 2007). This model contains a fast sodium current (Na f ; Seutin and Engel, 2010;Tucker et al, 2012), a sodium leak current (Na L ), a delayed rectifying potassium current (Liu et al, 2012;Khaliq and Bean, unpublished data), an A-type potassium current I A , an I H current (Z. M. Khaliq, unpublished data;Migliore et al, 2008), and the calcium-activated potassium channels, SK and BK (Hirschberg et al, 1998;Maylie et al, 2004;Evans et al, 2013;Jaffe et al 2011). In addition, the model contains five calcium channels (T, R, N, L 1.2 , and L 1.3 ; Tuckwell, 2012;Evans et al, 2013; Table 1).…”

“…Specifically, decay time constants ranging from 20 to 100 ms, and even up to 300 ms, have been observed in neurons of the nucleus of the tractus solitarii (Strube et al, 2015), tuberomammillary neurons (Jackson and Bean, 2007), globus pallidus and basal forebrain neurons (Baranauskas, 2004). Likewise, our data show a broad range of inactivation kinetics in mesoaccumbal neurons with many cells exhibiting atypically slow inactivating A-type potassium currents (average tau inactivation of mesoaccumbal neurons, ϳ98 ms), while mesostriatal neurons display a much narrower range of inactivating currents, consistent with data from unlabeled SNc dopamine neurons Amendola et al, 2012).…”

“…Postburst pauses may involve small-conductance, calcium-activated (SK) currents activated by increases in intracellular Ca2ϩ that result from highfrequency spiking or activation of metabotropic glutamate receptors (Fiorillo and Williams, 1998;Morikawa et al, 2003). In addition, it is likely that bursting neurons can experience pauses caused in part by Na ϩ channel inactivation during the refractory period (Tucker et al, 2012). Inhibitory pauses are also initiated as well as maintained to some extent by synaptic or modulatory inputs (Fiorillo and Williams, 1998;Gantz et al, 2013).…”

Nutritional status‐dependent endocannabinoid signalling regulates the integration of rat visceral information

“…Preparation of horizontal medullary slices was performed as described previously (Strube et al 2014). The brainstem was cut on a vibrating-blade microtome into 300-μm-thick slices, in oxygenated (95% O 2 -5% CO 2 , pH 7.4) saline containing the following (in mM): 130 NaCl, 3 KCl, 0.5 CaCl 2 , 4 MgCl 2 , 26 NaHCO 3 , 1.25 KH 2 PO 4 , 10 glucose, 0.5 ascorbate, 2 pyruvate and 3 myo-inositol.…”