title: Hypothyroidism decreases the ATP sensitivity of KATP channels from rat heart.
abstract: The effects of thyroid status on the properties of ATP-sensitive potassium channels were investigated. Single-channel recordings were made using excised inside-out membrane patches from enzymatically dissociated ventricular myocytes from hearts of control and thyroidectomized rats and each group was studied with and without administration of thyroid hormone. In patches excised from hypothyroid myocytes the IC50 for ATP inhibition of KATP channels was 110 micro m. This value was 3-fold higher than the IC50 in control myocytes (43 micro m). Treatment of hypothyroid rats to restore physiological levels of thyroid hormone (tri-iodothyronine, T3), resulted in a return to normal ATP-sensitivity (IC50 = 46 micro M). In patches from animals rendered hyperthyroid, the IC50 for ATP was 50 micro M and this value was not significantly different from the control. There was no difference in the cooperativity of ATP-binding (Hill coefficient, nH) among control (nH = 2.2), hypothyroid (nH = 2.1), T3-treated (nH = 2.0) and hyperthyroid groups (nH = 2.4). The unitary conductance was unchanged and there was no apparent change in intraburst kinetics between examples of single KATP channels from control and hypothyroid rats. Action potentials recorded in myocytes from hypothyroid rats were significantly shortened by 50 micro M levcromakalim, a KATP channel opener (P < 0.001) but unchanged in control myocytes.We conclude that hypothyroidism significantly decreased the ATP-sensitivity of KATP channels, whereas the induction of hyperthyroid conditions did not alter the ATP-sensitivity of these channels. Thus, hypothyroidism is likely to have important physiological consequences under circumstances in which KATP channels are activated, such as during ischemia.
authors.affiliation: Department of Physiology and Biophysics, University of Calgary, Alberta, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Light
authors.forename: Y
authors.initials: Y
authors.lastname: Shimoni
authors.forename: S
authors.initials: S
authors.lastname: Harbison
authors.forename: W
authors.initials: W
authors.lastname: Giles
authors.forename: R J
authors.initials: RJ
authors.lastname: French
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D019806:Cromakalim / Q000494:pharmacology; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000166:cytology; D007037:Hypothyroidism / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; D014284:Triiodothyronine; D019806:Cromakalim; D000255:Adenosine Triphosphate