Acute exposure to thyroid hormone increases Na+ current and intracellular Ca2+ in cat atrial myocytes.
Whole-cell recording methods and fluorescence microscopy were used to study the effects of acute exposure to thyroid hormone (T(3)) on cat atrial myocytes. Acute exposure ( approximately 5 min) to 10 nM T(3) significantly increased tetrodotoxin (TTX)-sensitive inward Na(+) current (I(Na)) at voltages between -40 and +20 mV. At maximal I(Na) activation (-40 mV) T(3) increased peak I(Na) by 32 %. T(3) had no effect on the time course of I(Na) decay, voltage dependence of activation, inactivation, or recovery from inactivation. Comparable exposures to reverse T(3) (rT(3)) or T(4) had no effect on I(Na). L-type Ca2+ current was unaffected by acute exposure to T(3). T(3)-induced increases in I(Na) were unaffected by 50 microM nickel, a blocker of T-type Ca2+ current. T(3) significantly increased cell shortening (+62 %) and could elicit spontaneous action potentials arising from Ca2+ -mediated after-depolarizations. T(3) (but not rT(3)) significantly increased baseline intracellular Ca2+, release of Ca2+ from sarcoplasmic reticulum (SR) and caffeine (10 mM)-induced release of SR Ca2+. We conclude that acute T(3) exposure increases Na(+) influx via I(Na) and thereby stimulates reverse-mode Na(+)-Ca2+ exchange to increase intracellular Ca2+ content and release. As a result, T(3) increases contraction strength, and can initiate Ca2+ -mediated arrhythmic activity. Acute non-genomic effects of T(3) can contribute to the positive inotropy and sinus (atrial) tachycardia traditionally attributed to chronic, genomic effects of elevated thyroid hormone on atrial muscle.
Wang
Yong G
YG
Department of Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA.
Dedkova
Elena N
EN
Fiening
Jon P
JP
Ojamaa
Kaie
K
Blatter
Lothar A
LA
Lipsius
Stephen L
SL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D004553:Electric Conductivity; D005260:Female; D006325:Heart Atria; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D015222:Sodium Channels; D014284:Triiodothyronine; D002110:Caffeine; D013779:Tetrodotoxin; D002118:Calcium