title: Increased number of myocardial voltage-gated Ca2+ channels and unchanged total beta-receptor number in long-term streptozotocin-diabetic rats.
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.
authors.affiliation: Institute of Clinical and Experimental Research, University of Aarhus, Denmark.
authors.forename: L B
authors.initials: LB
authors.lastname: Gøtzsche
authors.forename: N
authors.initials: N
authors.lastname: Rosenqvist
authors.forename: H
authors.initials: H
authors.lastname: Grønbaek
authors.forename: A
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: O
authors.initials: O
authors.lastname: Gøtzsche
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004594:Electrophysiology; D005260:Female; D015640:Ion Channel Gating; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D013974:Thyroxine