The effect of verapamil and EGTA on the rat phrenic nerve-hemidiaphragm preparation.
Relatively high concentrations of verapamil or EGTA [ethylene glycol-bis (beta-aminoethyl ether) N, N, N',N'-tetra acetic acid] inhibit contraction (P) of the rat phrenic nerve-hemidiaphragm preparation elicited by direct or indirect stimulation. The inhibitory effect of verapamil is greater (P less than 0.002) with direct (I50 = 26.3 +/- 1.7 microM) than indirect = I50 = 37.6 +/- 1.9 microM) stimulation. For EGTA the reverse is true: I50 is 1320 +/- 80 microM with direct and 1100 +/- 60 microM with indirect stimulation. The greater than 90% verapamil-induced depression of P can only be partially reversed by washout. Increasing the [Ca2+] or the addition of 4-aminopyridine (4AP) has insignificant antagonist effect. Except for the antagonism by 4AP during direct stimulation, the EGTA-induced depression of P is better antagonized by washout, increase of the [Ca2+], or the addition of 4AP than that caused by verapamil. Neostigmine did not antagonize the depression of P caused by either verapamil or EGTA. The findings presented indicate that the primary site of action of verapamil is postjunctional and that of EGTA is prejunctional.
Bikhazi
G B
GB
Flores
C
C
Foldes
F F
FF
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003964:Diaphragm / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology*; D004558:Electric Stimulation; D005026:Ethylene Glycols / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D000631:Aminopyridines; D005026:Ethylene Glycols; D009388:Neostigmine; D004533:Egtazic Acid; D015761:4-Aminopyridine; D014700:Verapamil; D002118:Calcium