Hormonal Signaling Actions on Kv7.1 (KCNQ1) Channels

2021 ◽  
Vol 61 (1) ◽  
pp. 381-400
Author(s):  
Emely Thompson ◽  
Jodene Eldstrom ◽  
David Fedida
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Cardiac Action Potential ◽  
Resting Membrane Potential ◽  
Voltage Gated ◽  
M Current ◽  
Kv7 Channels ◽  
Cardiac Action ◽  
Repolarization Phase ◽  
And Control

Kv7 channels (Kv7.1–7.5) are voltage-gated K+ channels that can be modulated by five β-subunits (KCNE1–5). Kv7.1-KCNE1 channels produce the slow-delayed rectifying K+ current, IKs, which is important during the repolarization phase of the cardiac action potential. Kv7.2–7.5 are predominantly neuronally expressed and constitute the muscarinic M-current and control the resting membrane potential in neurons. Kv7.1 produces drastically different currents as a result of modulation by KCNE subunits. This flexibility allows the Kv7.1 channel to have many roles depending on location and assembly partners. The pharmacological sensitivity of Kv7.1 channels differs from that of Kv7.2–7.5 and is largely dependent upon the number of β-subunits present in the channel complex. As a result, the development of pharmaceuticals targeting Kv7.1 is problematic. This review discusses the roles and the mechanisms by which different signaling pathways affect Kv7.1 and KCNE channels and could potentially provide different ways of targeting the channel.

Detection of takeoff potential from intracellular recordings

1982 ◽  
Vol 242 (6) ◽  
pp. H1115-H1117
Author(s):  
R. McGillivray ◽  
R. W. Wald
Keyword(s):  
Electrical Stimulation ◽  
Membrane Potential ◽  
Action Potential ◽  
Cardiac Action Potential ◽  
Intracellular Recordings ◽  
Purkinje Fibers ◽  
Cardiac Action ◽  
Cardiac Purkinje Fibers ◽  
Cardioactive Drugs

The measurement of takeoff potential from intracellular recordings of the cardiac action potential may be useful in the study of the cardiac action potential may be useful in the study of spontaneous automaticity and of the effects of cardioactive drugs on active propagation. We describe a circuit capable of detecting and storing the membrane potential at a point where the slope of the membrane potential exceeds a preset value. The capability of this circuit to track the takeoff potential was tested using intracellular recordings from cardiac Purkinje fibers during spontaneous automaticity as well as during electrical stimulation.

In Vitro  Electrophysiologic Effects of Morphine in Rabbit Ventricular Myocytes

2005 ◽  
Vol 103 (2) ◽  
pp. 280-286 ◽  
Author(s):  
Guo-Sheng Xiao ◽  
Jing-Jun Zhou ◽  
Guan-Ying Wang ◽  
Chun-Mei Cao ◽  
Gui-Rong Li ◽  
...  
Keyword(s):  
Action Potential ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Ventricular Myocytes ◽  
Cardiac Action Potential ◽  
Resting Membrane Potential ◽  
Opioid Receptor Antagonist ◽  
Cardiac Action ◽  
K Current ◽  
Rabbit Ventricular Myocytes

Background Morphine is widely used in patients undergoing surgical operations and is also reported to mediate cardioprotection of preconditioning. The current study determined effects of morphine at therapeutic to pharmacologic concentrations on cardiac action potential, L-type Ca2+ current (ICa.L), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1) in isolated rabbit ventricular myocytes. Methods Ventricular myocytes were enzymatically isolated from rabbit hearts. Action potential and membrane currents were recorded in current and voltage clamp modes. Results Morphine at concentrations from 0.01 to 1 microM significantly prolonged cardiac action potential, and at 0.1 and 1 microM slightly but significantly hyperpolarized the resting membrane potential. In addition, morphine at 0.1 microM significantly augmented ICa.L (at +10 mV) from 5.9 +/- 1.9 to 7.3 +/- 1.7 pA/pF (by 23%; P < 0.05 vs. control) and increased IK1 (at -60 mV) from 2.8 +/- 1.0 to 3.5 +/- 0.9 pA/pF (by 27%; P < 0.05 vs. control). Five microM naltrindole (a selective delta-opioid receptor antagonist) or 5 microM norbinaltorphimine (a selective kappa-opioid receptor antagonist) prevented the increase in ICa.L induced by morphine, but 5 microM CTOP (a selective mu-opioid receptor antagonist) did not. The three types of opioid antagonists did not affect the augmentation of IK1 by morphine. Morphine had no effect on IK. Conclusions These results indicate that morphine prolongs action potential duration by increasing ICa.L, an effect mediated by delta- and kappa-opioid receptors. It also hyperpolarizes cardiac resting membrane potential by increasing IK1, which is not mediated by opioid receptors.

Effects of temperature on cardiac transmembrane potentials in hibernation

1976 ◽  
Vol 230 (2) ◽  
pp. 403-409 ◽  
Author(s):  
HK Jacobs ◽  
FE South
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Papillary Muscle ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Prolonged Action ◽  
Transmembrane Potentials ◽  
Effects Of Temperature ◽  
And Control ◽  
Potential Parameters

Resting and action potential parameters were measured from papillary muscle isolated from hibernating and control hamsters and from rats. The temperature range of the study was 12-38 degrees C. The decrease in resting membrane potential (Em) with decreasing temperature was significantly less in the hibernation preparations (HH), down to 20 degrees C, than in either the control hamsters or rats. Below 20 degrees C the declines in Em of all preparations were indistinguishable. Action potential magnitude was adequately maintained in HH to 12 degrees C while both control hamster and rat action potentials declined markedly as temperatures were reduced. Both types of hamster preparations showed greatly prolonged action potentials with reduced temperatures as contrasted to a limited prolongation of rat action potentials. The data are suggestive of a membrane modication in hibernation.

Contribution of a swelling-activated chloride current to changes in the cardiac action potential

1997 ◽  
Vol 273 (2) ◽  
pp. C541-C547 ◽  
Author(s):  
J. I. Vandenberg ◽  
G. C. Bett ◽  
T. Powell
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
Resting Membrane Potential ◽  
Cardiac Action ◽  
Cell Recording ◽  
Induced Changes

The purpose of this investigation was to determine to what extent the swelling-activated Cl- current (ICl,swell) contributes to swelling-induced changes in the resting membrane potential and action potential duration (APD) in ventricular myocytes. Action potentials were recorded from guinea pig ventricular myocytes using conventional whole cell recording techniques. Cell swelling caused initial lengthening followed by a variable shortening of APD. In 59% of cells this secondary APD shortening had a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive component, consistent with a contribution from ICl,swell. Furthermore, DIDS partially antagonized the depolarization of the resting membrane potential that occurred during cell swelling. We have modeled the ICl,swell using the Oxsoft Heart computer program. Action potential changes predicted by the model agree well with the observed DIDS-sensitive component of the change in the action potential during cell swelling. We conclude that activation of ICl,swell contributes to shortening of APD and depolarization of the resting membrane potential during cell swelling in cardiac myocytes.

Ionic Basis of the Resting Membrane Potential and Action Potential in the Pharyngeal Muscle of Caenorhabditis elegans

2002 ◽  
Vol 87 (2) ◽  
pp. 954-961 ◽  
Author(s):  
Christopher J. Franks ◽  
Darrel Pemberton ◽  
Irina Vinogradova ◽  
Alan Cook ◽  
Robert J. Walker ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Voltage Gated ◽  
C Elegans ◽  
Current Voltage ◽  
Prolongation Of Action Potential ◽  
Ionic Basis

The pharynx of C. elegans is a rhythmically active muscle that pumps bacteria into the gut of the nematode. This activity is maintained by action potentials, which qualitatively bear a resemblance to vertebrate cardiac action potentials. Here, the ionic basis of the resting membrane potential and pharyngeal action potential has been characterized using intracellular recording techniques. The resting membrane potential is largely determined by a K+permeability, and a ouabain-sensitive, electrogenic pump. As previously suggested, the action potential is at least partly dependent on voltage-gated Ca2+ channels, as the amplitude was increased as extracellular Ca2+ was increased, and decreased by L-type Ca2+ channel blockers verapamil and nifedipine. Barium caused a marked prolongation of action potential duration, suggesting that a calcium-activated K+ current may contribute to repolarization. Most notably, however, we found that action potentials were abolished in the absence of external Na+. This may be due, at least in part, to a Na+-dependent pacemaker potential. In addition, the persistence of action potentials in nominally free Ca2+, the inhibition by Na+ channel blockers procaine and quinidine, and the increase in action potential frequency caused by veratridine, a toxin that alters activation of voltage-gated Na+channels, point to the involvement of a voltage-gated Na+ current. Voltage-clamp analysis is required for detailed characterization of this current, and this is in progress. Nonetheless, these observations are quite surprising in view of the lack of any obvious candidate genes for voltage-gated Na+ channels in the C. elegans genome. It would therefore be informative to re-evaluate the data from these homology searches, with the aim of identifying the gene(s) conferring this Na+, quinidine, and veratridine sensitivity to the pharynx.

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