Thyroid hormone increases the conductance density of f-channels in rabbit sino-atrial node cells.
In hyperthyroidism, the main cardiac manifestation is an increase in resting heart rate with a great degree of sinus tachycardia. As the pacemaker current, I(f), is reputed to be the main ionic mechanism involved in sinus rhythm, the objective of this study was to investigate the effect of triiodothyronine (T3) on I(f), in sino-atrial (SA) node cells isolated from rabbit heart, using the patch-clamp technique in whole-cell configuration. In cells incubated for 5-7 h in a medium containing 1 microM T3, the hormone increased I(f) by rising the maximal conductance without inducing shift of the activation curve or change in the reversal potential. The mean values of I(f) density (42.05+/-5.93 pA/pF, n = 13) and maximal conductance density (854.25+/-124.83 pS/pF, n = 16) were significantly increased compared with those measured in untreated cells (20.21+/-2.53 pA/pF, n = 14; 392.69+/-54.95; pS/pF, n = 16). In cells treated with T3, 0.1 microM isoprenaline, a beta-adrenergic agonist, was still able to induce a positive shift of the voltage dependence of I(f) activation. Reverse T3, the inactive form of T3, used in the same conditions, had no effect on I(f). According to the results, it was suggested that the acceleration of resting heart rate observed in hyperthyroidism, might be the consequence of a T3-induced stimulation of f-channel transcription in SA node myocytes.
Renaudon
B
B
Universite de Pointers/CNRS UMR 6558, France.
Lenfant
J
J
Decressac
S
S
Bois
P
P
D000818:Animals; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology*
D007473:Ion Channels; D014284:Triiodothyronine