[Effects of amiloride on calcium current in thyroxine-induced hypertrophied rat heart].
OBJECTIVE
The L-Type calcium currents were investigated in normal, hypertrophied and amiloride-treated rat ventricular myocytes so as to clarify the possible cause of the action potential lengthening that has been reported in thyroxine-induced hypertrophy. The interactions between agents such as thyroxine, Ang II and phenylephrine which induced hypertrophy with amiloride on the calcium current were analyzed.


METHODS
Myocardial hypertrophy was induced by i.p. L-thyroxine in rats. The cell length, cell width and cell area were measured by image analysis technique. For recording ICaL, the whole cell patch clamp technique was used. Potassium currents were suppressed by replacing K+ ions with Cs+ ions in intracellular media, and sodium current was blocked by 50 mumol.L-1 tetrodotoxin.


RESULTS
The Ca2+ current was found to be larger in hypertrophied cells (783pA) than in normal cells (433pA) and in amiloride-treated cells (429pA). However, no significant difference was observed in current density (6.54, 8.33, 5.74 pA/pF) in normal, hypertrophied and amiloride-treated cells. ICa displayed the same voltage dependence in three cell types. The potential giving 50% of activation (V1/2) moved towards more negative and the slope of activation curve was smaller in hypertrophied cells than in normal cells and amiloride cells. When expressed as percentages, the maximal increases in ICa were obtained with 1 mumol.L-1 Ang II and 100 mumol.L-1 phenylephrine in normal cells (+45.5% and +81.8%). Thyroxine 100 mumol.L-1 showed no effect on ICa. After giving amiloride, Ang II and phenylephrine did not increase the amplitude of ICa.


CONCLUSIONS
At the dose of 0.5 mg.kg-1.d-1, amiloride (p.o.) was shown to prevent the amplitude of ICa from increasing and to be effective against increases of amplitude of ICa by Ang II and phenylephrine.
Cheng
L
L
Department of Pharmacology, Tongji Medical University, Wuhan 430030, China.
Li
X H
XH
Yao
W X
WX
Xia
G J
GJ
Jiang
M X
MX
D000584:Amiloride / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D002469:Cell Separation; D005260:Female; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine
D020746:Calcium Channels, L-Type; D000804:Angiotensin II; D000584:Amiloride; D013974:Thyroxine