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- Title
β<sub>3</sub>-Adrenergic regulation of an ion channel in the heart—inhibition of the slow delayed rectifier potassium current <F>I<sub>Ks</sub></F> in guinea pig ventricular myocytes
- Authors
Bosch, Ralph F.; Schneck, Alexander C.; Kiehn, Johann; Zhang, Wei; Hambrock, Annette; Eigenberger, Bernd W.; Rüb, Norman; Gogel, Jeannette; Mewis, Christian; Seipel, Ludger; Kühlkamp, Volker
- Abstract
<B>Objectives:</B> <F>IKs</F>, the slow component of the delayed rectifier potassium current, underlies a strong β-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in <F>IKs</F>. Recent work has pointed to an opposing biological effect of β1- and β3-adrenoceptors in the heart. However the role of these subtypes in the regulation of cardiac ion channel function is unknown. <B>Methods:</B> We investigated the effects of β1- and β3-adrenoceptor modulation on <F>IKs</F> in guinea-pig ventricular myocytes, using patch-clamp techniques. <B>Results:</B> Superfusion with 100 nmol/l isoproterenol increased the step current amplitude by 81.3±8.0%. In contrast, after block of β1- (1 μmol/l atenolol) and β2-receptors (1 μmol/l ICI118,551), isoproterenol induced a reduction of the step current amplitude by 34.3±3.5%. The β3-selective agonist BRL37344 significantly reduced the <F>IKs</F> step current at +70 mV in a concentration-dependent manner (IC50: 5.01 nmol/l). In the presence of bupranolol (β1-, β2- and β3-adrenoceptor antagonist), the effect of BRL37344 was markedly attenuated, from 27.3±5.6% (100 nmol/l BRL37344 alone) to 4.0±1.3% (100 nmol/l BRL37344+1 μmol/l bupranolol). BRL37344 (100 μmol/) did not alter current amplitudes of KvLQT1/minK expressed in CHO cells or in Xenopus oocytes, excluding a direct effect of BRL37344 on the channel. 1 μmol/l BRL37344 mildly prolonged action potentials in guinea pig ventricle (APD90:+7.8%) <B>Conclusions:</B> We have demonstrated a functional coupling between the β3-adrenoceptor and ion channel function in the mammalian heart. Our findings point to a potential role for β3-adrenoceptors in cardiac electrophysiology and pathophysiology.
- Subjects
ION channels; POTASSIUM channels; MUSCLE cells
- Publication
Cardiovascular Research, 2002, Vol 56, Issue 3, p393
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/S0008-6363(02)00601-6