Delayed rectifier potassium currents and Kv2.1 mRNA increase in hippocampal neurons of scopolamine-induced memory-deficient rats.
To explore the ionic mechanisms of memory deficits induced by cholinergic lesion, whole-cell patch clamp recording techniques in combination with single-cell RT-PCR were used to characterize delayed rectifier potassium currents (IK) in acutely isolated hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. Scopolamine could induce deficits in spatial memory of rats. The peak amplitude and current density of IK measured in hippocampal pyramidal neurons were increased from 1.2+/-0.6 nA and 38+/-19 pA/pF of the control group (n=12) to 1.8+/-0.5 nA and 62+/-24 pA/pF (n=48, P<0.01) of the scopolamine-treated group. The steady-state activation curve of IK was shifted about 8 mV (P<0.01) in the direction of hyperpolarization in scopolamine-treated rats. The mRNA level of Kv2.1 was increased (P<0.01) in the scopolamine-treated group, but there was no significant change of Kv1.5 mRNA level. The present study demonstrated for the first time that IK was enhanced significantly in hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. The increase of Kv2.1 mRNA expression in hippocampal pyramidal cells might be responsible for the enhancement of IK and could be the ionic basis of the memory deficits induced by scopolamine.
Zhong
Chong-Bo
CB
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Pan
Ya-Ping
YP
Tong
Xiao-Yong
XY
Xu
Xiang-Hua
XH
Wang
Xiao-Liang
XL
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051666:Kv1.5 Potassium Channel; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012601:Scopolamine / Q000494:pharmacology*; D051669:Shab Potassium Channels
C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D018727:Muscarinic Antagonists; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D012601:Scopolamine; D011188:Potassium