Electrophysiological, pharmacological and molecular profile of the transient outward rectifying conductance in rat sympathetic preganglionic neurons in vitro

Whyment, Andrew D.; Coderre, Elaine; Wilson, Jennifer M.; Renaud, Leo P.; O’Hare, Eugene; Spanswick, David

doi:10.1016/j.neuroscience.2010.12.061

Cited by 11 publications

(26 citation statements)

References 65 publications

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“…These observations are in line with the high sensitivity of nerves and relatively low sensitivity of the mesenteric arterial smooth muscle to 4-AP [29,30]. K V 1.5 channels were found in other nerves, such as in rat brain [31,32], in ganglia [33,34], in Schwann cell membrane [35], in human spinal roots [36] and, recently, in sympathetic preganglionic nerves [37]. However, the presence of the channel has not been investigated in nerve endings of vascular tissue up to now.…”

Section: Discussionsupporting

confidence: 82%

Neurogenic Contraction Induced by the Antiarrhythmic Compound, AVE 0118, in Rat Small Mesenteric Arteries

Kun

Seprényi

Varró

et al. 2014

Basic Clin Pharma Tox

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The purpose of this study was to investigate the vasoactivity of two inhibitors of potassium ion (K+) channels, a potential antiarrhythmic compound, AVE 0118, and 4‐aminopyridine (4‐AP). Basal and stimulated tones of rat small mesenteric arteries as well as the possible involvement of KV1.5 ion channel in the mechanism of vascular effect induced by the compounds were analysed. The standard organ bath technique for vascular tone and immunohistochemistry for the localization of ion channels in the arterial tissue were performed. Third‐ or fourth‐order branch of arterial segments was mounted in myographs for recording the isometric tension. AVE 0118 (10−5 M) and 4‐AP (10−5 M) modulated neither the basal tone nor the contraction induced by noradrenaline but increased the contraction evoked by electrical field stimulation, sensitive to the block of alpha‐1 adrenergic receptors. KV1.5 ion channel‐specific immunostaining demonstrated the presence of immunoreactive nerves, and Schwann‐cell‐specific (S100) immunostaining confirmed the presence of myelin sheath in rat small mesenteric arteries. The study supports an indirect, sympathetic effect of AVE 0118 similar to that of 4‐AP, which is mediated, at least in part, by blocking neuronal KV1.5 type potassium ion channels in the medio‐adventitial layer of rat small mesenteric artery.

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Section: Discussionsupporting

confidence: 82%

Neurogenic Contraction Induced by the Antiarrhythmic Compound, AVE 0118, in Rat Small Mesenteric Arteries

Kun

Seprényi

Varró

et al. 2014

Basic Clin Pharma Tox

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“…Secondly, there is little if any measurable I A at membrane potentials less than −60 mV, as its V 1/2 is quite positive (∼−36 mV) [68], and the excitability experiments in the present study were performed at membrane potentials more negative than −65 mV. Thirdly, 4-AP blocks neuronal I A in the low millimolar range, with an IC 50 of 1 to 2 mM [68], [69] (similar to the IC 50 of ∼1.5 mM reported in HEK293 cells expressing Kv4.3 channels [70]), and the concentration used to induce burst firing in the present study was 0.1 mM; at this concentration, I A is only blocked by 7% [69]. Finally, absence of I A (as would occur in the presence of full block) produces a very different pattern of activity (at least in a model thalamic cell [64]) than what we observed.…”

Section: Discussionmentioning

confidence: 66%

Targeted Deletion of Kcne2 Impairs HCN Channel Function in Mouse Thalamocortical Circuits

Ying

Kanda

et al. 2012

PLoS ONE

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BackgroundHyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate the pacemaking current, Ih, which regulates neuronal excitability, burst firing activity, rhythmogenesis, and synaptic integration. The physiological consequence of HCN activation depends on regulation of channel gating by endogenous modulators and stabilization of the channel complex formed by principal and ancillary subunits. KCNE2 is a voltage-gated potassium channel ancillary subunit that also regulates heterologously expressed HCN channels; whether KCNE2 regulates neuronal HCN channel function is unknown.Methodology/Principal FindingsWe investigated the effects of Kcne2 gene deletion on Ih properties and excitability in ventrobasal (VB) and cortical layer 6 pyramidal neurons using brain slices prepared from Kcne2 +/+ and Kcne2 −/− mice. Kcne2 deletion shifted the voltage-dependence of Ih activation to more hyperpolarized potentials, slowed gating kinetics, and decreased Ih density. Kcne2 deletion was associated with a reduction in whole-brain expression of both HCN1 and HCN2 (but not HCN4), although co-immunoprecipitation from whole-brain lysates failed to detect interaction of KCNE2 with HCN1 or 2. Kcne2 deletion also increased input resistance and temporal summation of subthreshold voltage responses; this increased intrinsic excitability enhanced burst firing in response to 4-aminopyridine. Burst duration increased in corticothalamic, but not thalamocortical, neurons, suggesting enhanced cortical excitatory input to the thalamus; such augmented excitability did not result from changes in glutamate release machinery since miniature EPSC frequency was unaltered in Kcne2 −/− neurons.Conclusions/SignificanceLoss of KCNE2 leads to downregulation of HCN channel function associated with increased excitability in neurons in the cortico-thalamo-cortical loop. Such findings further our understanding of the normal physiology of brain circuitry critically involved in cognition and have implications for our understanding of various disorders of consciousness.

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“…; Zimmerman & Hochman, ; Whyment et al . ). A notable difference, evident from our recordings, is that the resting potentials tend to be more depolarised (−52 mV) than has been found in vitro (average V m ranging from −44 to −62 with a median of −59 mV (Spanswick & Logan, , b ; Pickering et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Sah & McLachlan, ; Zimmerman & Hochman, ; Whyment et al . ), slow and fast after‐hyperpolarisations (AHPs; Yoshimura et al . , ; Spanswick & Logan, ; Sah & McLachlan, ), a T‐type low threshold calcium conductance (Yoshimura et al .…”

Section: Introductionmentioning

confidence: 99%

“…From in vitro spinal cord slice recording studies it is apparent, across a range of species, that SPNs have some characteristic intrinsic properties that are likely to be important in the integration of the descending and segmental synaptic drives, such as a powerful transient rectification (Yoshimura et al 1987b;Pickering et al 1991;Sah & McLachlan, 1995;Zimmerman & Hochman, 2010;Whyment et al 2011), slow and fast after-hyperpolarisations (AHPs; Yoshimura et al 1986aYoshimura et al , 1987bSpanswick & Logan, 1990b;Sah & McLachlan, 1995), a T-type low threshold calcium conductance (Yoshimura et al 1987a;Sah & McLachlan, 1995;Wilson et al 2002) and the ability to generate bursting discharge (Yoshimura et al 1987a;Spanswick & Logan, 1990a;Logan et al 1996). There is also evidence that these properties are not uniformly distributed and several authors have attempted to subdivide the SPNs on the basis of these properties (Spanswick & Logan, 1990b;Pickering et al 1991;Zimmerman & Hochman, 2010) but it has not been possible to identify these SPN characteristics as being associated with a particular end organ function.…”

Section: Introductionmentioning

confidence: 99%

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Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ

Stalbovskiy

Briant

Paton

et al. 2014

The Journal of Physiology

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Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart–brainstem preparation to make whole cell patch clamp recordings from T3–4 SPNs (n = 98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVClike, 39%) from cutaneous vasoconstrictor-like (CVClike, 28%) SPNs. The MVClike SPNs have higher baseline firing frequencies (2.52 ± 0.33 Hz vs. CVClike 1.34 ± 0.17 Hz, P = 0.007). The CVClike have longer after-hyperpolarisations (314 ± 36 ms vs. MVClike 191 ± 13 ms, P < 0.001) and lower input resistance (346 ± 49 MΩ vs. MVClike 496 ± 41 MΩ, P < 0.05). MVClike firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVClike SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs.

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Electrophysiological, pharmacological and molecular profile of the transient outward rectifying conductance in rat sympathetic preganglionic neurons in vitro

Cited by 11 publications

References 65 publications

Neurogenic Contraction Induced by the Antiarrhythmic Compound, AVE 0118, in Rat Small Mesenteric Arteries

Neurogenic Contraction Induced by the Antiarrhythmic Compound, AVE 0118, in Rat Small Mesenteric Arteries

Targeted Deletion of Kcne2 Impairs HCN Channel Function in Mouse Thalamocortical Circuits

Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ

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