Single-channel activity and expression of atrial L-type Ca(2+) channels in patients with latent hyperthyroidism.
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 Ca(2+) 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 Ca(2+) channel alpha(1)-subunits was increased more than threefold (P < 0.01). In contrast, sarco(endo)plasmic reticulum Ca(2+)-ATPase and phospholamban levels were not significantly changed. We only observed a trend toward increased sarco(endo)plasmic reticulum Ca(2+)-ATPase expression (P = 0.085). Function and expression of human atrial L-type Ca(2+) channels are increased in latent hyperthyroidism. These endocrine effects on the heart may be clinically relevant.
Kreuzberg
U
U
Department of Pharmacology, University of Cologne, 50931 Cologne, Germany.
Theissen
P
P
Schicha
H
H
Schröder
F
F
Mehlhorn
U
U
de Vivie
E R
ER
Bokník
P
P
Neumann
J
J
Grohé
C
C
Herzig
S
S
D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003327:Coronary Disease / Q000601:surgery; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology*; D006325:Heart Atria / Q000503:physiopathology; D006801:Humans; D006980:Hyperthyroidism / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000502:physiology; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000099211:Phospholamban
D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000099211:Phospholamban