Ethanol enhances inward rectification in rat locus ceruleus neurons by increasing the extracellular potassium concentration.
The effect of ethanol on the current-voltage relationship of rat locus ceruleus (LC) neurons was examined under voltage-clamp conditions in a totally submerged brain slice preparation. LC neurons have the classic K(+)-specific type of inward rectification (IR), which is blocked by Ba++ and Cs+. Ethanol (40-200 mM) was found to enhance IR in LC neurons; it increased both the maximal slope conductance and shifted the voltage range for activation of IR in the depolarizing direction. These effects of ethanol were concentration dependent and fully reversible on washout. When IR was blocked with Ba++ or intracellular acetate, ethanol increased the slope conductance of the linear current-voltage relationship but did not restore IR. Ethanol also reduced the amplitude of afterhyperpolarizations that follow individual action potentials and trains of action potentials in LC neurons. Ethanol caused a depolarizing shift in the K+ equilibrium potential and its effects on IR could be mimicked by an increase in the K+ concentration in the medium. Specifically, 100 mM ethanol, on average, shifted the K+ equilibrium potential by 6.3 mV and its enhancement of IR was mimicked by an increase in the external K+ of 0.5-0.7 mM. From these data, it was concluded that ethanol enhances IR in LC neurons by increasing the extracellular K+ concentration.
Osmanovic
S S
SS
Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago.
Shefner
S A
SA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000431:Ethanol; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium