Ca2+-Activated K+ Currents in Rat Locus Coeruleus Neurons Induced by Experimental Ischemia, Anoxia, and Hypoglycemia
Murai, Yoshinaka, Hitoshi Ishibashi, Susumu Koyama, and Norio Akaike. Ca2+-activated K+ currents in rat locus coeruleus neurons induced by experimental ischemia, anoxia, and hypoglycemia. J. Neurophysiol. 78: 2674–2681, 1997. 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 by 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 by 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 potentialwith carbonyl cyanide- p-trifluoromethoxyphenyl-hydrazone(FCCP) as experimental anoxia all induced a slowly developing outward current ( I OUT) 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( I NMDA-OUT) and prolonged the one-half recovery time of I NMDA-OUT. The reversal potentials of both I OUT and I NMDA-OUT were close to the K+ equilibrium potential ( E K) of −82 mV. Either charybdotoxin or tolbutamide inhibited the I OUT and I NMDA-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 one-half recovery time of the NMDA-induced increase in [Ca2+]i was prolonged. The I OUT induced by NaCN was inhibited by a continuous treatment of thapsigargin but not by ryanodine, indicating the involvement of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) store. These findings suggest that energy deficiency causes Ca2+ release from the IICR store and activates continuous Ca2+-activated K+ channels and transient ATP-sensitive K+ channels in acutely dissociated rat LC neurons.