B-S Chen1, H Peng, S-N Wu. 1. Institute of Basic Medical Sciences, National Cheng Kung University Medical College, No. 1, University Road, Tainan 70101, Taiwan, Republic of China.
Abstract
BACKGROUND: Dexmedetomidine (DEX), a selective agonist of alpha2-adrenergic receptors, is recognized to facilitate analgesia and anaesthesia in humans. Despite the potential for wide use, its effects on ion currents and membrane potential in neurones remain largely unclear. METHODS: We investigated the effects of DEX on ion channels in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP and in cultured cerebellar neurones. RESULTS: DEX suppressed the amplitude of delayed rectifier K+ current [I(K(DR))] in a concentration-dependent manner with an IC50 value of 4.6 microM in NG108-15 cells. No change in the steady-state inactivation of I(K(DR)) was evident in the presence of DEX. A minimal binding scheme was also used to evaluate DEX-induced block of I(K(DR)). Inhibition of I(K(DR)) by DEX was still observed in cells preincubated with yohimbine (10 microM) or efaroxan (10 microM). DEX depressed the peak amplitude of Na+ current (I(Na)), whereas it had minimal effect on L-type Ca2+ current. Under current-clamp configuration, DEX increased the duration of action potentials (APs). I(K(DR)) and I(Na) in response to AP waveforms were more sensitive to block by DEX than those elicited during rectangular pulses. In isolated cerebellar granule cells, DEX also effectively suppressed I(K(DR)). CONCLUSIONS: The effects of DEX are not limited to its interactions with alpha2-adrenergic receptors. Inhibitory effects on I(K(DR)) and I(Na) constitute one of the underlying mechanisms through which DEX and its structurally related compounds might affect neuronal activity in vivo.
BACKGROUND:Dexmedetomidine (DEX), a selective agonist of alpha2-adrenergic receptors, is recognized to facilitate analgesia and anaesthesia in humans. Despite the potential for wide use, its effects on ion currents and membrane potential in neurones remain largely unclear. METHODS: We investigated the effects of DEX on ion channels in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP and in cultured cerebellar neurones. RESULTS:DEX suppressed the amplitude of delayed rectifier K+ current [I(K(DR))] in a concentration-dependent manner with an IC50 value of 4.6 microM in NG108-15 cells. No change in the steady-state inactivation of I(K(DR)) was evident in the presence of DEX. A minimal binding scheme was also used to evaluate DEX-induced block of I(K(DR)). Inhibition of I(K(DR)) by DEX was still observed in cells preincubated with yohimbine (10 microM) or efaroxan (10 microM). DEX depressed the peak amplitude of Na+ current (I(Na)), whereas it had minimal effect on L-type Ca2+ current. Under current-clamp configuration, DEX increased the duration of action potentials (APs). I(K(DR)) and I(Na) in response to AP waveforms were more sensitive to block by DEX than those elicited during rectangular pulses. In isolated cerebellar granule cells, DEX also effectively suppressed I(K(DR)). CONCLUSIONS: The effects of DEX are not limited to its interactions with alpha2-adrenergic receptors. Inhibitory effects on I(K(DR)) and I(Na) constitute one of the underlying mechanisms through which DEX and its structurally related compounds might affect neuronal activity in vivo.