Prosper N'Gouemo1, Martin Morad. 1. Department of Pediatrics, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC, 20057, USA, pn@georgetown.edu.
Abstract
RATIONALE: Large conductance calcium-activated potassium (BK(Ca) or K(Ca)1.1) channels are well-known molecular targets for the action of alcohol and therefore may play an important role in the pathogenesis of alcohol withdrawal syndrome. OBJECTIVES: We evaluate the modifications of total outward K⁺ currents and protein expression of BK(Ca) channels α-subunit in inferior colliculus (IC) neurons obtained from controls and rats subjected to alcohol withdrawal associated with enhanced susceptibility to seizures. METHODS: Outward K⁺ currents and BK(Ca) channel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively. RESULTS: Total outward K⁺ current density was significantly reduced in IC neurons at 24 and 48 h during the alcohol withdrawal period when the susceptibility to seizures was maximal and absent, respectively. The iberiotoxin-sensitive (BK(Ca)) current density and conductance also were significantly reduced at 24 h following alcohol withdrawal. Consistent with functional data, the levels of protein expression of α-subunit associated with BK(Ca) channels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal. CONCLUSIONS: The downregulation of BK(Ca) channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BK(Ca) channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.
RATIONALE: Large conductance calcium-activated potassium (BK(Ca) or K(Ca)1.1) channels are well-known molecular targets for the action of alcohol and therefore may play an important role in the pathogenesis of alcohol withdrawal syndrome. OBJECTIVES: We evaluate the modifications of total outward K⁺ currents and protein expression of BK(Ca) channels α-subunit in inferior colliculus (IC) neurons obtained from controls and rats subjected to alcohol withdrawal associated with enhanced susceptibility to seizures. METHODS: Outward K⁺ currents and BK(Ca) channel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively. RESULTS: Total outward K⁺ current density was significantly reduced in IC neurons at 24 and 48 h during the alcohol withdrawal period when the susceptibility to seizures was maximal and absent, respectively. The iberiotoxin-sensitive (BK(Ca)) current density and conductance also were significantly reduced at 24 h following alcohol withdrawal. Consistent with functional data, the levels of protein expression of α-subunit associated with BK(Ca) channels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal. CONCLUSIONS: The downregulation of BK(Ca) channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BK(Ca) channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.
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