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

Abstract

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 α1-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.