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Inhibition of a TREK-like K+ channel current by noradrenaline requires both β1- and β2-adrenoceptors in rat atrial myocytes
- Source :
- Bond, R C, Choisy, S C M, Bryant, S M, Hancox, J C & James, A F 2014, ' Inhibition of a TREK-like K + channel current by noradrenaline requires both β 1-and β 2-adrenoceptors in rat atrial myocytes ', Cardiovascular Research, vol. 104, no. 1, pp. 206-15 . https://doi.org/10.1093/cvr/cvu192, Cardiovascular Research
- Publication Year :
- 2014
-
Abstract
- AIMS: 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).METHODS AND RESULTS: 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 β1-/β2-adrenoceptor antagonism (1 µM propranolol or 10 µM β1-selective atenolol and 100 nM β2-selective ICI-118,551 in combination), but not by β1- or β2-antagonist alone. The action of noradrenaline could be mimicked by β2-agonists (zinterol and fenoterol) in the presence of β1-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 β1-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD30 by 52 ± 19% (n = 5; P < 0.05), and this effect was abolished by combined β1-/β2-antagonism, but not by atenolol alone.CONCLUSION: Noradrenaline inhibits a rat atrial TREK-like K(+) channel current via a PTX-sensitive mechanism involving co-operativity of β1-/β2-adrenoceptors that contributes to atrial APD prolongation.
- Subjects :
- Male
K2P channel
Patch-Clamp Techniques
Time Factors
TREK-1
Physiology
Action Potentials
Pharmacology
chemistry.chemical_compound
Norepinephrine
Adrenergic beta-2 Receptor Antagonists
Myocyte
Myocytes, Cardiac
Zinterol
Arachidonic Acid
Adrenergic beta-1 Receptor Antagonists
Osmotic stretch
Arachidonic acid
Beta-adrenoceptor
Adrenergic beta-1 Receptor Agonists
Ion Channels and Arrhythmias
Cardiology and Cardiovascular Medicine
medicine.drug
Signal Transduction
medicine.medical_specialty
Calcium Channels, L-Type
Propranolol
Pertussis toxin
Potassium Channels, Tandem Pore Domain
Physiology (medical)
Internal medicine
Receptors, Adrenergic, beta
medicine
Potassium Channel Blockers
Animals
Steady-state outward current
Heart Atria
Rats, Wistar
Adrenergic beta-2 Receptor Agonists
Fenoterol
business.industry
Original Articles
Receptor Cross-Talk
Atenolol
Background K+ current
Endocrinology
chemistry
Receptors, Adrenergic, beta-1
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Bond, R C, Choisy, S C M, Bryant, S M, Hancox, J C & James, A F 2014, ' Inhibition of a TREK-like K + channel current by noradrenaline requires both β 1-and β 2-adrenoceptors in rat atrial myocytes ', Cardiovascular Research, vol. 104, no. 1, pp. 206-15 . https://doi.org/10.1093/cvr/cvu192, Cardiovascular Research
- Accession number :
- edsair.doi.dedup.....aa0fe13a8c80c44d979dbf701c4140be