Atsushi Nishiyama

Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle

OBJECTIVE Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through beta-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel alpha-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of beta-adrenergic signaling pathway in their expressions under both status. METHODS Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of L-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the beta-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay. RESULTS MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n = 6, p < 0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n = 6, p < 0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso. CONCLUSION Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through beta-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.

Downregulation of voltage-gated K+ channels in rat heart with right ventricular hypertrophy

The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K+ channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 ± 0.01 vs. 0.58 ± 0.03 ms ( n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 ± 2.6 ms vs. 31.5 ± 5.8 ms ( n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 ± 8.9 ms vs. 110.0 ± 4.2 ms ( n = 6); P < 0.05] and corrected Q-T interval [Q-Tc; control vs. MCT: 8.4 ± 0.7 ms vs. 10.2 ± 0.4 ms ( n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4.3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 ± 10, 76 ± 3, 58 ± 5, 81 ± 5, and 45 ± 12%, respectively ( n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 ± 0.28 vs. 0.88 ± 0.44 (arbitrary units) ( n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 ± 0.25 vs. 0.87 ± 0.18 ( n = 3), NS; Kv1.4: 1.0 ± 0.22 vs. 1.27 ± 0.37 ( n = 3), NS; Kv1.5: 1.0 ± 0.16 vs. 0.91 ± 0.28 ( n = 3), NS; Kv2.1: 1.0 ± 0.26 vs. 0.99 ± 0.25 ( n = 3), NS; Kv4.2: 1.0 ± 0.15 vs. 1.22 ± 0.28 ( n = 3), NS; Kv4.3: 1.0 ± 0.20 vs. 1.21 ± 0.28 ( n= 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K+ channels.The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K(+) channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 +/- 0.01 vs. 0.58 +/- 0.03 ms (n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 +/- 2.6 ms vs. 31.5 +/- 5.8 ms (n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 +/- 8.9 ms vs. 110.0 +/- 4.2 ms (n = 6); P < 0.05] and corrected Q-T interval [Q-T(c); control vs. MCT: 8.4 +/- 0. 7 ms vs. 10.2 +/- 0.4 ms (n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4. 3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 +/- 10, 76 +/- 3, 58 +/- 5, 81 +/- 5, and 45 +/- 12%, respectively (n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 +/- 0.28 vs. 0.88 +/- 0.44 (arbitrary units) (n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 +/- 0.25 vs. 0.87 +/- 0.18 (n = 3), NS; Kv1.4: 1.0 +/- 0.22 vs. 1.27 +/- 0.37 (n = 3), NS; Kv1.5: 1.0 +/- 0.16 vs. 0.91 +/- 0.28 (n = 3), NS; Kv2.1: 1.0 +/- 0.26 vs. 0.99 +/- 0.25 (n = 3), NS; Kv4.2: 1.0 +/- 0.15 vs. 1.22 +/- 0.28 (n = 3), NS; Kv4.3: 1.0 +/- 0.20 vs. 1.21 +/- 0.28 (n = 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K(+) channels.

Advanced atrioventricular block induced by obstructive sleep apnea before oxygen desaturation

We report a patient with transient advanced atrioventricular (AV) block induced by obstructive sleep apnea (OSA). This 54-year-old man was diagnosed as having severe OSA and AV block with ventricular asystole for more than 6 s during overnight polysomnography, which occurred just from the onset of OSA before oxygen desaturation had occurred. An electrophysiological study revealed normal AV conduction system function and normal His-Purkinje system function. The resolution of OSA with continuous positive airway pressure therapy improved the advanced AV block. Therefore, the bradyarrhythmia was determined to be an OSA-induced AV block that occurred before oxygen desaturation.