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Inhibition of a TREK-like K+ channel current by noradrenaline requires both ?1- and ?2-adrenoceptors in rat atrial myocytes.


ABSTRACT: Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (IKss).Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited IKss (IC50 = 0.90 nM, 42.1 ± 4.3% at 1 µM, n = 7) and potentiated the L-type Ca(2+) current (ICaL, EC50 = 136 nM, 205 ± 40% at 1 µM, n = 6). Noradrenaline-sensitive IKss was weakly voltage-dependent, time-independent, and potentiated by the arachidonic acid analogue, 5,8,11,14-eicosatetraynoic acid (EYTA; 10 µM), or by osmotically induced membrane stretch. Noise analysis revealed a unitary conductance of 8.4 ± 0.42 pS (n = 8). The biophysical/pharmacological properties of IKss indicate a TREK-like K(+) channel. The effect of noradrenaline on IKss was abolished by combined ?1-/?2-adrenoceptor antagonism (1 µM propranolol or 10 µM ?1-selective atenolol and 100 nM ?2-selective ICI-118,551 in combination), but not by ?1- or ?2-antagonist alone. The action of noradrenaline could be mimicked by ?2-agonists (zinterol and fenoterol) in the presence of ?1-antagonist. The action of noradrenaline on IKss, but not on ICaL, was abolished by pertussis toxin (PTX) treatment. The action of noradrenaline on ICaL was mediated by ?1-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD30 by 52 ± 19% (n = 5; P < 0.05), and this effect was abolished by combined ?1-/?2-antagonism, but not by atenolol alone.Noradrenaline inhibits a rat atrial TREK-like K(+) channel current via a PTX-sensitive mechanism involving co-operativity of ?1-/?2-adrenoceptors that contributes to atrial APD prolongation.

SUBMITTER: Bond RC 

PROVIDER: S-EPMC4174890 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Inhibition of a TREK-like K+ channel current by noradrenaline requires both β1- and β2-adrenoceptors in rat atrial myocytes.

Bond Richard C RC   Choisy Stéphanie C M SC   Bryant Simon M SM   Hancox Jules C JC   James Andrew F AF  

Cardiovascular research 20140909 1


<h4>Aims</h4>Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (IKss).<h4>Methods and results</h4>Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited IKss (IC50 = 0.90 nM, 42.1 ± 4.3%  ...[more]

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