[Effects of calcium channel blockers on electrical and mechanical responses of rat phrenic nerve-diaphragm preparations].
The effects of diltiazem, prenylamine and verapamil on the electrical and mechanical responses of a rat phrenic nerve-diaphragm preparation were investigated as a function of the indirect stimulating frequency. The amplitude of the muscle compound action potential was depressed by all three drugs with stimulation between 3 and 50 Hz. The contractile force of the diaphragm was increased by these drugs in concentrations of 3 x 10(-8)-3 x 10(-5) mol/l at low frequency (3-10 Hz), but the contractility was decreased at higher concentrations (above 3 x 10(-5) mol/l). In contrast, a facilitating effect was not observed at a higher stimulating frequency (above 20 Hz), but a concentration depressant effect did develop above 1 x 10(-6) mol/l. The literature data and our results suggest that low concentrations of calcium channel blocking agents can not influence the trigger calcium current at low frequency (under 15 Hz), but calcium liberation and the contractile force are increased by these drugs. The intracellular calcium liberation triggered by the calcium current or the muscle force was inhibited by these drugs at higher concentrations. Above 15 Hz, the liberated intracellular calcium is insufficient for the contraction, so an adequate quantity of calcium is obtained from the extracellular space. It is suggested that an adequate calcium uptake is inhibited at low concentrations of these drugs at higher frequency, and the contractility is thereby inhibited.
Zupko
I
I
Szent-Györgyi Albert Orvostudományi Egyetem, Gyógyszerhatástani Intézet, Szeged.
Blazsó
G
G
Minker
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D011299:Prenylamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D011299:Prenylamine
Kalcium-csatorna blokkolók hatása patkány nervus phrenicus-diaphragma preparátum elektromos és mechanikus válaszára.