AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 278: H723-H730, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 3, H723-H730, March 2000

Single-channel activity and expression of atrial L-type Ca2+ channels in patients with latent hyperthyroidism

U. Kreuzberg1, P. Theissen2, H. Schicha2, F. Schröder1, U. Mehlhorn3, E. R. de Vivie3, P. Bokník4, J. Neumann4, C. Grohé5, and S. Herzig1

Departments of 1 Pharmacology, 2 Nuclear Medicine, and 3 Cardiothoracic Surgery, University of Cologne, 50931 Cologne; 4 Department of Pharmacology, University of Münster, 48149 Münster; and 5 Medizinische Poliklinik, University of Bonn, 53105 Bonn, Germany

Patients with "latent hyperthyroidism" (suppressed thyroid-stimulating hormone and normal circulating thyroid hormones) are at risk to develop atrial fibrillation. In animal models, hyperthyroidism is associated with increased cardiac L-type Ca2+ current. Therefore, we assessed L-type channel function and expression in right atria from patients undergoing cardiac surgery. Single L-type channels were studied in the cell-attached condition. Voltage dependence of gating was similar in patients with and without latent hyperthyroidism. With use of a pulse protocol leading to maximum channel availability, single-channel activity was further analyzed. Average peak current was significantly enhanced in latent hyperthyroidism, mainly because of an increased channel availability (P < 0.05). Protein expression was analyzed by Western blot. In latent hyperthyroidism, expression of Ca2+ channel alpha 1-subunits was increased more than threefold (P < 0.01). In contrast, sarco(endo)plasmic reticulum Ca2+-ATPase and phospholamban levels were not significantly changed. We only observed a trend toward increased sarco(endo)plasmic reticulum Ca2+-ATPase expression (P = 0.085). Function and expression of human atrial L-type Ca2+ channels are increased in latent hyperthyroidism. These endocrine effects on the heart may be clinically relevant.

human myocytes; patch clamp; phospholamban; sarco(endo)plasmic reticulum calcium-adenosinetriphosphatase; Western blot


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