Inward currents elicited by metabolic inhibition in rat dorsal vagal neurones

University College London 2006 (2006) Proc Physiol Soc 3, PC149

Poster Communications: Inward currents elicited by metabolic inhibition in rat dorsal vagal neurones

Robert H Balfour1, Stefan Trapp1

1. Dept of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London, United Kingdom.

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A proportion of dorsal vagal neurones (DVN) have been shown to respond to metabolic inhibition (MI) with a KATP channel-mediated outward current [1,2]. Here we show that MI also elicits small inward currents in DVN. Brainstem slices (200 μm) were obtained from juvenile Sprague-Dawley rats. After 30min recovery at 34°C, slices were kept at 22°C in artificial cerebrospinal fluid (ACSF). Whole-cell recordings were used to assess the response to metabolic inhibition elicited by bath application of either 1 mM cyanide (1-3 min), 3 mM azide (1-3 min) or glucose-free ACSF (hypoglycaemia; 5-30 min). MI-induced a KATP channel-mediated outward current in 16 DVN [see 1,2]. Prior to the development of the KATP current, an inward current was observed. This current was also seen in 45 neurones without functional KATP channels. It was small (-30±3 pA at –70 mV holding potential; mean ± 1 s.e.m.; n=24) with a fast onset (90±4 s; n=40) for azide and cyanide. In contrast, for hypoglycaemia the onset was 184±48 s (n=4) in non-glucose-sensors and 38±11 s (n=3) in glucose-sensors [2]. Analysis of the current-voltage relations revealed that MI induced a decrease of conductance in some DVN. This conductance had a reversal potential (Rev) close to EK (-95±4 mV; n=5) and was well described by the Goldman-Hodgkin-Katz equation, indicating an openly rectifying K+ channel. In the remaining cells MI led to an increase in conductance with a Rev between -65 and 10 mV; n=24). An inward current of -17±4 pA at -70 mV pA, onset of 100±20 s, (n=3) with Revs of -30, -45 and -100 mV was seen in response to MI in 0 mM [Ca2+]o. Using 143 mM instead of 5 mM [Cl]i an inward current of -18±4 pA at -70 mV with an onset of 100±27 s and Revs of -25, -50 and of -92 mV, was elicted by MI. Na+/K+ ATPase inhibition (100 µM strophanthidin or 50 µM ouabain) produced an inward current of -43±6 pA at -70 mV (n=7). The amplitude of this current was not significantly different from that elicited by MI (paired t test, p>0.05). However, the current induced by Na+/K+ ATPase inhibition showed no Rev within -20 to -120 mV. In summary, DVN responded to MI either with a decrease of an openly rectifying K+ conductance or an increase in conductance, which was not mediated by Cl or Ca2+, but may be due in part to inhibition of the Na+/K+ ATPase. The onset of current in response to mitochondrial inhibition was significantly faster (p<0.01) than in response to hypoglycaemia and glucose-sensors responded much faster than non-glucose-sensors. These results suggest that glucose-sensors are more sensitive to MI and that [ATP]i is the key mediator for the electrical responses.



Where applicable, experiments conform with Society ethical requirements.

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