DITPA restores the repolarizing potassium currents Itof and Iss in cardiac ventricular myocytes of diabetic rats.
Diabetes Mellitus (DM) can produce an increase in the cardiac action potential duration and QT interval that can be associated with sudden death. These cardiac effects are due to a region-specific decrease in repolarizing outward K(+) currents. Some authors have suggested that the proarrhythmic effects of diabetes can be due to diabetes-induced hypothyroidism. Thus, we have examined the effect of the thyroid hormone analog diiodothyropropionic acid (DITPA) on calcium-independent outward potassium currents in ventricular myocytes from diabetic rats. Sustained (I(ss)) and fast transient outward (I(tof)) K(+) currents were recorded using the whole-cell configuration of the patch-clamp technique. Myocytes were enzymatically isolated from the free wall of the right ventricle, and the epicardial and endocardial layers of the left ventricle of healthy, diabetic and DITPA-treated diabetic rats. Circulating thyroid hormones were measured by electrochemiluminescence. DITPA-treatment of diabetic rats restored I(tof) and I(ss) current densities in cardiac myocytes from the three regions studied, but did not alter current densities in myocytes of control rats. T(3) and T(4) levels were reduced by diabetes, and DITPA-treatment increased circulating T(3) levels. T(3)-treatment of diabetic rats also restored current densities to control values. However, direct incubation of diabetic myocytes with DITPA did not restore current densities. In summary, DITPA-treatment of diabetic rats restored the potassium current (I(tof) and I(ss)) densities in myocytes from all ventricular regions.
Ferrer
Tania
T
Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Col., México.
Gallego
Mónica
M
Madrigal-Quiñónez
Rafael
R
Torres-Jácome
Julián
J
Navarro-Polanco
Ricardo
R
Cásis
Oscar
O
Sánchez-Chapula
José A
JA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002469:Cell Separation; D003627:Data Interpretation, Statistical; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004104:Diiodothyronines / Q000494:pharmacology*; D007037:Hypothyroidism / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood
D001786:Blood Glucose; D004104:Diiodothyronines; D015221:Potassium Channels; D011422:Propionates; D013963:Thyroid Hormones; C082182:3,5-diiodothyropropionic acid