Attenuated inhibition of L-type calcium currents by troglitazone in fructose-fed rat cardiac ventricular myocytes.
We recently reported that troglitazone, an insulin-sensitizing agent, inhibited l-type Ca current (ICa,L) more effectively in streptozotocin (STZ)-induced diabetic ventricular myocytes than in age-matched control myocytes. However, whether this agent would effectively inhibit ICa,L in an animal model of hyperinsulinemia is unknown. Using whole-cell voltage-clamp techniques, ICa,L was measured in ventricular myocytes isolated from 12 to 16 weeks on fructose-enriched feeding and age-matched control rats. Under control conditions, fructose-fed myocytes did not differ from control myocytes in membrane capacitance, current density, or voltage-dependent properties of ICa,L. Troglitazone inhibited ICa,L in both control and fructose-fed myocytes in a concentration-dependent manner. However, this inhibition was less in fructose-fed than in control myocytes; the half-maximum inhibitory concentrations of troglitazone measured at a holding potential of -50 mV were 16.9 and 9.8 micromol/L, respectively. Contrary to the STZ-induced diabetic rat, the suppressive effect of troglitazone on cardiac ventricular ICa,L was attenuated in fructose-fed rats. Persistent elevation of plasma insulin concentration may play a role in these processes.
Arikawa
Masaya
M
Department of Internal Medicine 1, Oita University, Oita, Japan.
Takahashi
Naohiko
N
Kira
Tetsuya
T
Hara
Masahide
M
Yoshimatsu
Hironobu
H
Saikawa
Tetsunori
T
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D004032:Diet; D004594:Electrophysiology; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D020746:Calcium Channels, L-Type; D002839:Chromans; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D005632:Fructose; D000077288:Troglitazone