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. 1995 Aug 15;487(Pt 1):37–50. doi: 10.1113/jphysiol.1995.sp020859

KATP channel mediation of anoxia-induced outward current in rat dorsal vagal neurons in vitro.

S Trapp 1, K Ballanyi 1
PMCID: PMC1156597  PMID: 7473257

Abstract

1. Thin brainstem slices (150 microns thickness) were taken from mature rats, and membrane potentials (Em) and currents (Im) in the dorsal vagal neurons (DVN) were analysed with whole-cell patch clamp techniques during anoxia. 2. At a holding potential (Vh) of -50 mV, a sustained anoxia-induced outward current (AOC) of 92 +/- 44 pA (reversal potential (Erev), -78 +/- 12 mV) and a concomitant increase of membrane conductance (gm) from 2.2 +/- 0.45 to 5.9 +/- 2.4 nS were revealed in 40% of 142 DVN analysed. The AOC led to a hyperpolarization of the cells by 14.4 +/- 6.1 mV from a mean resting Em of -51 +/- 6 mV, and to blockade of spontaneous action potential discharges. In the remaining DVN, anoxia had almost no effect on Em, Im or gm and did not block spontaneous action potential discharges. 3. The AOC was not affected by 0.5 microM tetrodotoxin (TTX), 2 mM Mn2+, 50 microM cyanonitroquinoxaline dione (CNQX) or 100 microM bicuculline. 4. Elevation of the extracellular [K+] from 3 to 10 mM resulted in a positive shift of Erev of the AOC by 23 mV, whereas an increase in the [Cl-] of the patch pipette solution from 5 to 144 mM had no effect on Erev. 5. In DVN responding with an AOC, addition of 200 microM diazoxide, an activator of ATP-sensitive K+ (KATP) channels, to oxygenated solutions elicited a similar outward current (Erev = -79 +/- 5.5 mV, n = 12) and increase in gm. Diazoxide did not affect Em, Im or gm in cells which did not show an AOC. 6. In a subpopulation of DVN (n = 26), spontaneous activation of a KATP current with an Erev of -80 +/- 6 mV was observed. As analysed in four of these cells, an AOC was revealed during the initial phase of development of the spontaneous outward current but not under steady-state conditions. 7. The AOC, the diazoxide-induced current, and the spontaneous outward current were completely blocked upon bath application of the KATP channel blocker tolbutamide (100-200 microM). 8. The results indicate that the sustained anoxia-induced outward current of dorsal vagal neurons is due to activation of KATP channels. A possible physiological role of functional inactivation of these cells during metabolic disturbances is discussed.

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Selected References

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