Assessing the long-term role of L-type voltage dependent calcium channel blocker verapamil on short-term presynaptic plasticity at dentate gyrus of hippocampus.
High-voltage-activated Ca(2+) channels on presynaptic nerve terminals are known to play an important role in neurotransmitter release at both excitatory and inhibitory synapses. Whereas there is currently debate over the contribution of L-type voltage dependent Ca(2+) channels (L-type VDCCs) on the short-term presynaptic plasticity which is a defining feature of neuronal activity, the underlying mechanisms are poorly understood. In the present study, the L-type VDCCs chronically was inhibited with different doses of verapamil (10, 20 and 50 mg/kg; orally) to evaluate hippocampal dentate gyrus (DG) inhibitory interneuron function and its involvement on short-term plasticity using paired pulse stimulation in perforant path-DG of hippocampus. Our data show that chronic oral treatment of verapamil at dose of 50 mg/kg but not at lower doses, facilitated the excitability of DG cells at inter-stimulus intervals 20, 30 and 50 ms (P<0.03, 0.01 and 0.001; respectively) in population spike amplitude ratio, which is indicative of paired pulse potentiation in perforant path-DG synapses. While there are no significant differences in field excitatory postsynaptic potential slope ratio at all doses. We suggest that DG neurons facilitation is caused by inhibition of inhibitory interneurons directly and/or indirectly via inhibition of glutamate release in hippocampal DG. Therefore, these experiments indicate that chronic use of verapamil has effect on short-term presynaptic plasticity.
Lashgari
Reza
R
Neuroscience Research Center and Department of Physiology, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. rezalashgari@ipm.ir
Motamedi
Fereshteh
F
Noorbakhsh
Seyed-Mohammad
SM
Zahedi-Asl
Saleh
S
Komaki
Alireza
A
Shahidi
Siamak
S
Haghparast
Abbas
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D018709:Statistics, Nonparametric; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil