Gr. Li et Cm. Baumgarten, Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias, AM J P-HEAR, 280(1), 2001, pp. H272-H279
Citations number
41
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Gd3+ blocks stretch-activated channels and suppresses stretch-induced arrhy
thmias. We used whole cell voltage clamp to examine whether effects on Nachannels might contribute to the antiarrhythmic efficacy of Gd3+. Gd3+ inhi
bited Na+ current (I-Na) in rabbit ventricle (IC50 = 48 muM at -35 mV, hold
ing potential -120 mV), and block increased at more negative test potential
s. Gd3+ made the threshold for INa more positive and reduced the maximum co
nductance. Gd3+ (50 muM) shifted the midpoints for activation and inactivat
ion of I-Na 7.9 and 5.7 mV positive but did not alter the slope factor for
either relationship. Activation and inactivation kinetics were slowed in a
manner that could not be explained solely by altered surface potential. Par
adoxically, Gd3+ increased I-Na under certain conditions. With membrane pot
ential held at -75 mV, Gd3+ still shifted threshold for activation positive
, but INa increased positive to -40 mV, causing the current-voltage curves
to cross over. When availability initially was low, increased availability
induced by Gd3+ dominated the response at test potentials positive to -40 m
V. The results indicate that Gd3+ has complex effects on cardiac Na+ channe
ls. Independent of holding potential, Gd3+ is a potent I-Na blocker near th
reshold potential, and inhibition of I-Na by Gd3+ is likely to contribute t
o suppression of stretch-induced arrhythmias.