Tetraethylammonium-Sensitive ventricular repolarization in diabetic rat myocardium: effects of rosiglitazone

To examine ventricular action-potential responses to tetraethylammonium (TEA), a non-selective potassium-channel blocker, in streptozotocin-induced diabetic rats and determine whether rosiglitazone modifies these responses.

Male Wistar rats were assigned to Control (C), Control plus Rosiglitazone (C+RSG), Diabetic (D), or Diabetic plus Rosiglitazone (D+RSG) groups. Diabetes was induced with streptozotocin (45 mg/kg, intravenous). Resting membrane potential (RMP), action potential amplitude (APA), and half-repolarization time (½RT) were recorded from isolated left ventricular papillary muscles before and after TEA administration (2 mmol/L).

At week 8, blood glucose was 563 ± 29 mg/dL in diabetic rats and 98 ± 6 mg/dL in controls (p < 0.001). Rosiglitazone reduced the diabetic value to 336 ± 25 mg/dL (p < 0.05 vs. D). TEA increased ½RT from 18 ± 1 to 38 ± 2 ms in controls (+20 ms) and from 60 ± 3 to 65 ± 3 ms in diabetic myocardium (+5 ms). Diabetic preparations had higher post-TEA ½RT because repolarization was prolonged at baseline; however, the absolute TEA-associated increment was smaller than in controls. TEA also increased APA in untreated control and diabetic preparations.

Diabetes was associated with marked baseline prolongation of ventricular repolarization. The smaller absolute ½RT increment in diabetic myocardium does not support enhanced TEA responsiveness. Because TEA is non-selective, the findings reflect an integrated response to TEA-sensitive potassium conductances rather than dysfunction of a specific current subtype. Rosiglitazone modified selected electrophysiological responses without normalizing diabetic repolarization.