Role of ion channels and intraterminal calcium homeostasis in the action of deltamethrin at presynaptic nerve terminals.

TitleRole of ion channels and intraterminal calcium homeostasis in the action of deltamethrin at presynaptic nerve terminals.
Publication TypeJournal Article
Year of Publication1989
AuthorsClark JM, Brooks MW
JournalBiochemical pharmacology
Volume38
Issue14
Pagination2233-45
Date Published1989 Jul 15
AbstractUsing a continuous perfusion system, synaptosomes prepared from rat brain released [3H]norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10(-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10(-5) M), a phenethylamine-type calcium channel blocker, inhibited 21%. In combination, these two specific ion channel antagonists appear to function independently of each other in an additive fashion. Addition of deltamethrin to this preparation resulted in an enhanced release of [3H]norepinephrine which occurred in a biphasic fashion. At 10(-7) M, deltamethrin produced a 42% enhancement in the first or initial peak of [3H]norepinephrine release and a 100% enhancement in the second or tailing peak. Addition of deltamethrin to tetrodotoxin-pretreated synaptosomes resulted in a net 37% enhancement of the initial peak release and a net increase of 277% in the tailing peak. Addition of deltamethrin to D595-pretreated synaptosomes produced no significant effect on enhanced [3H]norepinephrine release from either peak. Since tetrodotoxin is a specific sodium channel blocker, deltamethrin may be enhancing [3H]norepinephrine release by increasing the uptake of Ca2 via other voltage-gated channels (e.g. calcium) or exchange mechanisms in addition to its action at voltage-gated sodium channels. To determine whether deltamethrin may also have an effect on intraterminal Ca2+ homeostasis, external Ca2+ was replaced with Ba2+ and synaptosomes were depolarized with pentylenetetrazole (PTZ). At 10(-5) M, deltamethrin produced a 66% increase in neurotransmitter release over that produced by PTZ alone. An estimated EC50 value of deltamethrin for PTZ-induced release was calculated to be 2.4 x 10(-10) M.
Alternate JournalBiochem. Pharmacol.