Effect of manganese on guinea pig ventricle: initial depression and late augmentation of contractile force.
Effects of Mn2+ on isolated guinea pig ventricular myocardia were examined. In isolated papillary muscles, Mn2+ produced a transient decrease in contractile force followed by a late sustained augmentation. Mn2+ markedly increased the amplitude of post-rest contractions; the time course of potentiation was almost the same as that of the late augmentation of contractile force after Mn2+ application. Mn2+ also increased the amplitude of rapid-cooling contractures. The negative inotropic effect of diltiazem and nicardipine was not affected by the presence of Mn2+. Mn2+ shortened the action potential duration under normal condition whereas it prolonged the duration under Ca2+ free conditions. Mn2+, when applied to fura-2-loaded ventricular myocytes, markedly quenched the cytoplasmic fluorescence excited at 360 nm wavelength. We concluded that Mn2+ not only causes a decrease in contractile force by blocking the L-type Ca2+ channel, but also enters the cytoplasm through the channel and produces late augmentation of the contractile force through enhancement of sarcoplasmic reticulum function.
Tanaka
Hikaru
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan. htanaka@phar.toho-u.ac.jp
Ishii
Tadashi
T
Fujisaki
Ryoichi
R
Miyamoto
Yusuke
Y
Tanaka
Yoshino
Y
Aikawa
Tokiko
T
Hirayama
Wataru
W
Kawanishi
Toru
T
Shigenobu
Koki
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D016276:Ventricular Function
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D008345:Manganese; D009529:Nicardipine; D004110:Diltiazem