Inhibitory effects of 1,4-DHP antagonists on synaptic GABA release modulated by BAY-K 8644 in mechanically dissociated rat substantia innominata.
The effects of dihydropyridine (1,4-DHP) agonist and antagonists on miniature inhibitory postsynaptic currents (mIPSCs) were investigated in mechanically dissociated rat substantia innominata neurons attached to native GABAergic presynaptic nerve terminals, namely 'synaptic bouton preparation', using nystatin perforated patch recording mode under voltage-clamp conditions. BAY-K 8644 (BAY-K), an L-type Ca(2+) channel agonist, reversibly and concentration dependently facilitated the GABAergic mIPSC frequency without altering the distribution of current amplitudes. Removal of extracellular Ca(2+) completely suppressed the facilitatory effect of BAY-K on mIPSC frequency. The facilitatory effect of BAY-K on mIPSC frequency was maintained even in the presence of selective N-, P- and Q-type Ca(2+) channel antagonists, such as 3 x 10(-6) M omega-conotoxin-GVIA (omega-CgTX-GVIA), 3 x 10(-8) M omega-agatoxin-IVA (omega-AgTX-IVA) and 3 x 10(-6)M omega-conotoxin-MVIIC (omega-CmTX-MVIIC). However, nicardipine (3 x 10(-6) M) and nimodipine (3 x 10(-6) M), 1,4-DHP antagonists, significantly inhibited the mIPSC frequency enhanced by BAY-K by 37 +/- 5 and 42 +/- 6%, respectively. These results suggest the possible existence of L-type Ca(2+) channels in GABAergic presynaptic nerve terminals.
Watanabe
Yasuo
Y
Department of Pharmacology/Anesthesiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. yasuwatnb@aol.com
Wang
Zhi Ming
ZM
Rhee
Jeong Seop
JS
Lawlor
George F
GF
Ishibashi
Hitoshi
H
Akaike
Norio
N
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013377:Substantia Innominata / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat