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Effects of SO_2 derivatives on transient outward K~+ and delayed rectifier K~+ currents in acutely isolated rat hippocampal CA_1 neurons

SANG Nan MENG Zi-Qiang (Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China)  
In order to investigate possible mechanisms through which SO 2 affects the central neuronal system (CNS), we examined the effects of SO 2 derivatives on the transient outward K+ (I A) and delayed rectifier K+ currents (I K) in freshly dissociated hippocampal CA 1 rat neurons using whole-cell patch clamp techniques. Single rat hippocampal CA 1 neurons were acutely isolated by enzymatic digestion and mechanical dispersion from 7-10-day-old wistar rats. Cells with a pyramidal shaped soma, short dendrites and axons were chosen for study and used within 3 h after dissociation. Whole-cell patch clamp recordings were made with an Axopatch 200B patch clamp amplifier (Axon Instruments, USA); cells were held at a holding potential (HP) of 100 mV and a series of 160 ms depolarizing steps to +90 mV (10 mV increment at each step) were applied at a frequency of 0.5 Hz. Evoked currents were filtered at 2 kHz, digitized at 1.67 kHz, and stored in PC 586 computer using a digidata 1 200B interface (Axon Instruments, USA) and pCLAMP version 6.0.4 software (Axon Instruments, USA). Capacity transients were canceled and series resistance was compensated (70%) using the internal circuitry of Axopatch 200B. All experiments were conducted at room temperature (20-25℃). All data were analyzed by the use of pCLAMP CLAMPFIT procedures (Axon Instruments) and Origin 5.0 (Microcal software, USA). Results were presented as ±SD, and statistical comparisons were made using Student's t-test. Upon the administration of SO 2 derivatives, the amplitudes of I A and I K were increased incrementally in doses from 1 to 100 μM. Half-increase doses were 26.19 μmol/L and 14.50 μmol/L, respectively. In addition, the increase in the amplitudes of I A and I K was different at different membrane potentials, but was not markedly changed at different frequencies. The results indicate that SO 2 derivatives reversibly increased the amplitudes of I A and I K in a dose-dependent and voltage-dependent, but not frequency-dependent manner. Before and after the application of 10 μM SO 2 derivatives, the half-activation voltage of I A were 7.18±6.19 mV and 5.93±12.96 mV (n=10, P0.05), with k of -24.20±3.48 mV and -23.87±2.66 mV (n=10, P0.05); the half-activation voltage of I K were 17.64±7.31 mV and 13.43±2.00 mV (n=10, P0.01), with k of 18.66±2.12 mV and 22.26±7.55 mV (n=10, P0.05). In addition, upon the administration of SO 2 derivatives, a positive shift of the inactivation curve of I A occurred along the potential axis (control V h=-65.93±1.97 mV, 10 μM SO 2 derivatives V h=-59.22±3.83 mV, n=10, P0.01). However, the slope factors k (control 15.67±3.13 mV, 10 μM SO 2 derivatives 16.37±0.98 mV, n=10, P0.05) remained unchanged. The results indicated that the activation process of I A was not affected by SO 2 derivatives, but, in accordance with the incremental action of SO 2 derivatives on I A and I K, the activation of I K was promoted and the inactivation process of I A was partially inhibited. The results suggest that SO 2 derivatives increase the amplitudes of I A and I K, promote the activation of I K, and inhibit the inactivation of I A, which might increase the efflux of intracellular K+ through K+ channels, causing the decrease of intracellular K+ concentration which in turn induces functional disorders of the central neurons and mediates neuronal apoptosis. The results imply that SO 2 derivatives are damaging to the CNS and that SO 2 pollution in the atmosphere is related to the CNS diseases [Acta Zoologica Sinica 49(1):73-79, 2003].
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