Related Experiment Video
Updated: Jul 15, 2025

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Activation of neurokinin-III receptors modulates human atrial TASK-1 currents
Felix Wiedmann1, Amelie Paasche1, Jendrik Nietfeld2
1Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg /Mannheim, University of Heidelberg, Heidelberg, Germany; HCR, Heidelberg Center for Heart Rhythm Disorders, University Hospital Heidelberg, Heidelberg, Germany.
Rationale:
The neurokinin-III receptor was recently shown to regulate atrial cardiomyocyte excitability by inhibiting atrial background potassium currents. TASK-1 (hK2P3.1) two-pore-domain potassium channels, which are expressed atrial-specifically in the human heart, contribute significantly to atrial background potassium currents. As TASK-1 channels are regulated by a variety of intracellular signalling cascades, they represent a promising candidate for mediating the electrophysiological effects of the Gq-coupled neurokinin-III receptor.
Objective:
To investigate whether TASK-1 channels mediate the neurokinin-III receptor activation induced effects on atrial electrophysiology.
Methods And Results:
In Xenopus laevis oocytes, heterologously expressing neurokinin-III receptor and TASK-1, administration of the endogenous neurokinin-III receptor ligands substance P or neurokinin B resulted in a strong TASK-1 current inhibition. This could be reproduced by application of the high affinity neurokinin-III receptor agonist senktide. Moreover, preincubation with the neurokinin-III receptor antagonist osanetant blunted the effect of senktide. Mutagenesis studies employing TASK-1 channel constructs which lack either protein kinase C (PKC) phosphorylation sites or the domain which is regulating the diacyl glycerol (DAG) sensitivity domain of TASK-1 revealed a protein kinase C independent mechanism of TASK-1 current inhibition: upon neurokinin-III receptor activation TASK-1 channels are blocked in a DAG-dependent fashion. Finally, effects of senktide on atrial TASK-1 currents could be reproduced in patch-clamp measurements, performed on isolated human atrial cardiomyocytes.
Conclusions:
Heterologously expressed human TASK-1 channels are inhibited by neurokinin-III receptor activation in a DAG dependent fashion. Patch-clamp measurements, performed on human atrial cardiomyocytes suggest that the atrial-specific effects of neurokinin-III receptor activation on cardiac excitability are predominantly mediated via TASK-1 currents.
Related Concept Videos
Regulation of Heart Rates
The SNS increases heart rate through the release of norepinephrine and epinephrine, which act on beta-1 adrenergic receptors in the heart. This action increases the rate of depolarization in the sinoatrial (SA) node, the heart's...
G-Protein Gated Ion Channels
Sensory...
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Conduction System of the Heart
The pacemaker cells are located in two primary nodes: the sinoatrial (SA) node and the atrioventricular (AV) node. The SA node pacemaker cells can autonomously depolarize, triggering an action potential that leads to the...
Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they...
Mechanism of Cardiac Arrhythmias

