Inhibition of L-type voltage dependent calcium channels causes impairment of long-term potentiation in the hippocampal CA1 region in vivo

被引:57
作者
Freir, DB [1 ]
Herron, CE [1 ]
机构
[1] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dept Human Anat & Physiol, Dublin 2, Ireland
关键词
NMDA receptor; verapamil; D-AP5 anaesthetised rat; L-type agonist;
D O I
10.1016/S0006-8993(02)04190-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Long-term potentiation (LTP), in the hippocampal CA1 region is dependent on postsynaptic calcium influx. It is generally accepted that calcium influx occurs via activation of the NMDA receptor channel complex. However, studies in vitro using a high-frequency stimulus protocol ( greater than or equal to200 Hz) demonstrated previously an NMDA receptor-independent form of LTP that is dependent upon activation of L-type voltage-dependent calcium channels (VDCCs). Here we have investigated a role for L-type VDCCs in LTP in vivo. Two structurally different, L-type VDCC blockers, verapamil (1, 3 and 10 mg/kg) and diltiazem (1, 10 and 20 mg/kg), depressed the induction of LTP in a dose-dependent manner. Increased activation of L-type VDCCs by Bay K 8644, an L-type agonist, however, did not enhance LTP. The NMDA receptor antagonist D-AP5 (5 and 20 mM injected i.c.v) impaired, but failed to block fully LTP in vivo. A reduced level of LTP could still be recorded following co-administration of verapamil and D-AP5. The level of LTP recorded was similar to that observed in the presence of either verapamil (10 mg/kg) or D-AP5 alone. These results suggest that activation of the NMDA receptor/channel and L-type VDCCs are involved in the induction of LTP in area CA1 in vivo. However, it appears that activation of other receptor/channels may also play a role in this form of LTP. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:27 / 36
页数:10
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