Ca2+-activated K+ currents in rat locus coeruleus neurons induced by experimental ischemia, anoxia and hypoglycemia. YOSHINAKA MURAI, HITOSHI ISHIBASHI, SUSUMU KOYAMA, AND NORIO AKAIKE. Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan.
APStracts 4:156N, 1997.
ABSTRACT
The effects of metabolic inhibition on membrane currents and N-methyl-D- aspartic acid (NMDA)-induced currents were investigated in dissociated rat locus coeruleus (LC) neurons using the nystatin perforated patch recording mode under voltage-clamp conditions. Changes in the intracellular Ca2+ concentration ([Ca2+]i) during the metabolic inhibition were also investigated using the microfluometry with a fluorescent probe, Indo-1. Removal of both the oxygen and glucose (experimental ischemia), deprivation of glucose (hypoglycemia), and a blockade of electron transport by sodium cyanide (NaCN) or a reduction of the mitochondrial membrane potential with carbonyl cyanide- p-trifluoromethoxyphenyl-hydrazone (FCCP) as experimental anoxia, all induced a slowly developing outward current (IOUT) at a holding potential of -40 mV. The application of 10-4 M NMDA induced a rapid transient peak and a successive steady-state inward current, and a transient outward current immediately after washout. All treatments related to metabolic inhibition increased the NMDA- induced outward current (INMDA-OUT), and prolonged the half recovery time of INMDA-OUT. The reversal potentials of both IOUT and INMDA-OUT were close to the K+ equilibrium potential (EK) of -82 mV. Either charybdotoxin or tolbutamide inhibited the IOUT and INMDA-OUT, suggesting the contribution of Ca2+-activated and ATP-sensitive K+ channels, even though the inhibitory effect of tolbutamide gradually diminished with time. Under the metabolic inhibition, the basal level of [Ca2+]i was increased and the half recovery time of the NMDA-induced increase in [Ca2+]i was prolonged. The IOUT induced by NaCN was inhibited by a continuous treatment of thapsigargin but not by ryanodine, indicating the involvement of inositol 1,4,5-tris-phosphate (IP3)- induced Ca2+ release (IICR) store. These findings suggest that energy deficiency causes Ca2+ release from the IICR store and activates a continuous Ca2+-activated K+ channels and a transient ATP-sensitive K+ channels in acutely dissociated rat LC neurons. 

Received 17 July 1996; accepted in final form 14 July 1997.
APS Manuscript Number J563-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997