Rutecki P A
Department of Neurology, University of Wisconsin, Madison 53705, USA.
Epilepsy Res. 1995 Feb;20(2):125-36. doi: 10.1016/0920-1211(94)00078-b.
Norepinephrine has been proposed to have both pro- and anticonvulsant properties. In the CA3 region of rat hippocampal slices, we studied the effects of norepinephrine and selective adrenergic agonists and antagonists on spontaneously occurring epileptiform discharges produced by either picrotoxin, a convulsant that impairs GABAA-mediated inhibition, or by elevated extracellular potassium ([K+]o). Bath application of 5 microM norepinephrine (NE) increased the rate of discharges produced by 7.5 mM [K+]o but not the rate of picrotoxin-induced discharges. At higher concentrations (> or = 10 microM), NE slowed the rate of spontaneous epileptiform discharges produced by picrotoxin. Spontaneous discharges produced by either picrotoxin or 7.5 mM [K+]o were slowed or stopped by alpha-adrenergic receptor activation, the alpha 1 receptor being most responsible for this slowing effect. The alpha 2 agonist clonidine had minimal effects on the discharge rate; however, the alpha 2 antagonists yohimbine and idazoxan slowed the rate. In contrast, beta receptor or adenylate cyclase activation increased the rate of spontaneous discharges. This acceleration in rate was accompanied by a decrease in the amplitude and duration of the afterhyperpolarization (AHP) that follows the intracellularly recorded paroxysmal depolarizing shift (PDS). These results confirm that beta-adrenergic receptor activation increases the rate of epileptiform discharges and suggest that the acceleration is a result of a decrease in the AHP duration and amplitude. Activation of alpha-adrenergic receptors slowed the rate of epileptiform discharges without an associated change in the AHP. The AHP that follows the PDS helps define the maximal rate of epileptiform discharges in the hippocampal slice and a decrease in the duration of the AHP may contribute to the transition from an interictal to ictal pattern of epileptiform activity.
去甲肾上腺素被认为具有促惊厥和抗惊厥两种特性。在大鼠海马切片的CA3区域，我们研究了去甲肾上腺素以及选择性肾上腺素能激动剂和拮抗剂对由印防己毒素（一种损害GABAA介导的抑制作用的惊厥剂）或细胞外钾离子浓度升高（[K+]o）所产生的自发性癫痫样放电的影响。浴槽中加入5微摩尔/升的去甲肾上腺素（NE）可增加由7.5毫摩尔/升[K+]o所产生的放电频率，但不会增加印防己毒素诱导的放电频率。在更高浓度（≥10微摩尔/升）时，NE会减慢由印防己毒素所产生的自发性癫痫样放电的频率。由印防己毒素或7.5毫摩尔/升[K+]o所产生的自发性放电会因α-肾上腺素能受体激活而减慢或停止，其中α1受体对此减慢作用起主要作用。α2激动剂可乐定对放电频率影响极小；然而，α2拮抗剂育亨宾和咪唑克生会减慢放电频率。相反，β受体或腺苷酸环化酶激活会增加自发性放电频率。这种频率的加快伴随着细胞内记录的阵发性去极化偏移（PDS）之后的超极化后电位（AHP）的幅度和持续时间的减小。这些结果证实β-肾上腺素能受体激活会增加癫痫样放电频率，并表明这种加快是AHP持续时间和幅度减小的结果。α-肾上腺素能受体激活会减慢癫痫样放电频率，而AHP无相关变化。PDS之后的AHP有助于确定海马切片中癫痫样放电的最大频率，AHP持续时间的减小可能有助于癫痫样活动从发作间期模式转变为发作期模式。
