Increased number of myocardial voltage-gated Ca2+ channels and unchanged total β-receptor number in long-term streptozotocin-diabetic rats

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Abstract
In order to elucidate further the abnormal myocardial Ca2+ metabolism in diabetes mellitus, voltage-gated Ca2+ channels and beta-receptors were quantified in myocardial membranes of short- and long-term diabetic rats. Diabetes was induced by an injection of streptozotocin (STZ). Animals were killed 2, 4, 7, 90 and 200 days after STZ. A group of diabetic animals were treated with insulin for 20 days following 180 days of untreated diabetes. Diabetic animals developed low triiodothyronine syndrome. During short-term diabetes, the maximum binding capacity (MBC) for Ca2+ channels was reduced by 25% at day 4 (p < 0.05) and the beta-receptor MBC was reduced by 48% (p < 0.05). A normalizing tendency was observed at day 7 for both receptor types; insulin-treated rats did not differ from controls at that time. After 90 and 200 days of untreated diabetes the Ca2+ channel MBC had increased by 36% and 27%, respectively (p < 0.05). Twenty days of strictly regulated blood glucose following 180 days of untreated diabetes totally normalized the Ca2+ channel MBC. This is in contrast to a previous report where insulin treatment did not normalize the Ca2+ channel MBC. Total beta-receptor MBCs did not differ from control values 90 and 200 days after STZ. In conclusion, an increase in rat myocardial Ca2+ channel MBC during long-term diabetes was fully normalized by short-term insulin treatment. The increase in sarcolemmal Ca2+ channels could serve to compensate for a defect coupling of the beta-receptor to adenylate cyclase. An elevated Ca2+ channel number may, at least theoretically, lead to increased Ca2+ flow across the cardiac sarcolemma and in this way contribute to the diabetic cardiomyopathy by increasing the intracellular Ca2+ concentration.

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