Premium
Effects of Development and Thyroid Hormone on K + Currents and K + Channel Gene Expression in Rat Ventricle
Author(s) -
Wickenden A. D.,
Kaprielian R.,
Parker T. G.,
Jones O. T.,
Backx P. H.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.271be.x
Subject(s) - ventricle , medicine , myocyte , endocrinology , stimulation , chemistry , gene expression , thyroid , electrophysiology , biology , gene , biochemistry
1 In rat heart, three K + channel genes that encode inactivating transient outward ( I TO )‐like currents are expressed. During development the predominant K + channel mRNA species switches from Kv1.4 to Kv4.2 and Kv4.3. However, no functional correlate of this isoform switch has been reported. We investigated action potential characteristics and I TO in cultured neonatal rat ventricular myocytes and adult rat hearts. We further examined whether the changes in K + channel gene expression and the associated electrophysiology that occurs during development could be induced by thyroid hormone. 2 In myocytes isolated from right ventricle of adult rat heart, action potential duration was short and independent of rate of stimulation. The density of I TO was 21.5 ± 1.8 pA pF −1 ( n = 21 ). Recovery from inactivation was best described by a single exponential (τ fast = 31.7 ± 2.7 ms, n = 13 ). The current remaining at the end of a 500 ms pulse ( I SUS ) was 6.2 ± 0.5 pA pF −1 ( n = 19 ). 3 In contrast to adult cells, action potential duration was prolonged and was markedly rate dependent in cultured neonatal rat ventricular myocytes. The current density of I TO measured in cultured ventricular myocytes from 1‐ to 2‐day‐old rats was 10.1 ± 1.5 pA pF −1 ( n = 17 ). The recovery from inactivation for I TO was best described by the sum of two exponentials (τ fast = 64.3 ± 8.8 ms, 54.4 ± 10.2%; τ slow = 8216 ± 2396 ms, 37.4 ± 7.9%; n = 5 ). I SUS was 4.4 ± 0.6 pA pF −1 ( n = 17 ). Steady‐state activation and inactivation were similar in adult and neonatal ventricular myocytes. 4 In neonatal myocytes treated with thyroid hormone, tri‐iodothyronine (T 3 , 100 n m ), action potential duration was abbreviated and independent of stimulation rate. Whilst T 3 did not significantly increase I TO density (24.0 ± 2.9 pA pF −1 ; n = 21 in T 3 treated cells cf. 20.1 ± 3.0 pA pF −1 ; n = 37 in untreated controls), the recovery from inactivation of I TO was accelerated (τ fast = 39.2 ± 3.6 ms, 82.2 ± 8.9%, n = 9 ). T 3 did however, increase I SUS current density (4.7 ± 0.77 pA pF −1 ; n = 37 and 7.0 ± 0.7 pA pF −1 , n = 21 , in control and T 3 treated cells, respectively). 5 The effects of T 3 (100 n m ) were associated with a marked decrease in the expression of Kv1.4 at the mKNA and protein level, and an increase in the expression of Kv4.3 without changes in Kv4.2 mRNA levels. 6 The findings of the present study indicate that postnatal development involves a shortening of action potential duration and an increase in the density of I TO . Furthermore, we show that development is also associated with a loss of action potential rate dependence, and an acceleration in the rate of recovery of I TO . We propose that these functional effects occur as a consequence of the previously reported developmental Kv1.4 to Kv4.2/Kv4.3 isoform switch. In cultured neonatal myocytes, T 3 induced many of the electrophysiological and molecular changes that normally occur during postnatal development, suggesting that this hormone may play an important role in postnatal electrophysiological development.