Membrane stretch augments the cardiac muscarinic K+ channel activity

Pleumsamran, Apisate; Kim, D

doi:10.1007/bf00235046

Cited by 28 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypo‐osmolar stress inactivates the heteromeric Kir3.4 channel expressed in Xenopus oocytes 34 . Stretch activates the cardiac G protein (GK)‐gated, muscarinic K + acetylcholine (KACh) channel if ACh is present and this appears to be independent of receptor/G protein, probably via a direct effect on the channel protein/lipid bilayer 35 …”

Section: At the Channel Levelmentioning

confidence: 99%

Mechanosensitive‐Mediated Interaction, Integration, and Cardiac Control

Lab

2006

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

This review covers aspects of the cardiac mechanotransduction field at different levels, and advocates the possibility that mechanoelectro-chemical transduction forms part of a network of mechanically linked integration in heart-mechanically mediated integration (MMI). It assembles evidence and observations in the literature to promote this hypothesis. Mechanical components can provide the bond between interactions at molecular, cellular, and macro levels to enable the integration. Stretch-activated channels (SACs) exist in the heart, but stresses and strains can affect other membrane channels or receptors. A cellular mechanical change can thus promote several ionic or downstream changes. Cell signal cascades have been implicated and can affect membrane electrophysiology. MMI could shape intracellular and downstream signals using the cytoskeleton and intracellular Ca(2+). MMI also spans other regulatory systems and processes such as the autonomic nervous system (ANS) and operates throughout the whole heart as an integrative system. Finally, supporting the hypothesis, if elements of the normal integration become deranged it contributes to cardiovascular disease and, potentially, lethal arrhythmia.

show abstract

Section: At the Channel Levelmentioning

confidence: 99%

Mechanosensitive‐Mediated Interaction, Integration, and Cardiac Control

Lab

2006

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…A prime candidate for an effect of stretch on muscarinic slowing is the muscarinic (acetylcholine; ACh)‐activated potassium channel (K ACh and its current, I K,ACh ), present in the SAN pacemaker cells. It has been shown that I K,ACh is mechanosensitive 10–12 . Normally, significant I K,ACh occurs briefly following the release of ACh from varicosities along the parasympathetic nerve fibres running though the SAN.…”

Section: Introductionmentioning

confidence: 99%

Tertiapin‐Q removes a mechanosensitive component of muscarinic control of the sinoatrial pacemaker in the rat

Han

Wilson

Bolter

2010

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. In an isolated right atrial preparation, an increase in right atrial pressure (RAP) produces an increase in atrial rate. This rate response is larger and occurs faster when there is background vagal or muscarinic stimulation. 2. We hypothesized that in the latter situation, an increase in RAP antagonizes the effect of muscarinic stimulation through stretch inactivation of the mechanosensitive muscarinic potassium current I(K,ACh). 3. In two groups of bath-mounted right atria isolated from male Wistar rats (control n = 12; 300 nmol/L tertiapin-Q treated (to block I(K,ACh)) n = 10), we examined the change in atrial rate when RAP was raised from 2 to 8 mmHg; oxotremorine-M (oxo-M; from 10 to 500 nmol/L) was added to incrementally activate muscarinic receptors. 4. In both control and tertiapin-Q-treated groups, oxo-M reduced atrial rate, but its effect was less ( approximately 40-50%) in the latter group (P < 0.001). In control preparations, responses to an increase in RAP became progressively larger and quicker as the concentration of oxo-M was increased, whereas in tertiapin-Q treated preparations oxo-M did not affect either the amplitude or the speed of the response (P < 0.0001 for both). 5. The results support the hypothesis that atrial stretch antagonizes muscarinic slowing by its effect on I(K,ACh). We suggest that through this mechanism, parasympathetic control of heart rate may be modulated continuously by RAP.

show abstract

“…35). Mechanosensitivity of the K ACh channels has been also reported (36,37). We therefore tested whether actin is also associated with the macromolecular channel complex.…”

Section: Fig 2 Composition Of Girk1 Signaling Complexmentioning

confidence: 99%

Coordination of Membrane Excitability through a GIRK1 Signaling Complex in the Atria

Nikolov

Ivanova-Nikolova

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Control of heart rate is a complex process that integrates the function of multiple G protein-coupled receptors and ion channels. Among them, the G protein-regulated inwardly rectifying K ؉ (GIRK or K ACh ) channels of sinoatrial node and atria play a major role in beat-tobeat regulation of the heart rate. The atrial K ACh channels are heterotetrameric proteins that consist of two pore-forming subunits, GIRK1 and GIRK4. Following m 2 -muscarinic acetylcholine receptor (M2R) stimulation, K ACh channel activation is conferred by the direct binding of G protein ␤␥ subunits (G␤␥) to the channel. Here we show that atrial K ACh channels are assembled in a signaling complex with G␤␥, G protein-coupled receptor kinase, cyclic adenosine monophosphatedependent protein kinase, two protein phosphatases, PP1 and PP2A, receptor for activated C kinase 1, and actin. This complex would enable the K ACh channels to rapidly integrate ␤-adrenergic and M2R signaling in the membrane, and it provides insight into general principles governing spatial integration of different transduction pathways. Furthermore, the same complex might recruit protein kinase C (PKC) to the K ACh channel following ␣-adrenergic receptor stimulation. Our electrophysiological recordings from single atrial K ACh channels revealed a potent inhibition of G␤␥-induced channel activity by PKC, thus validating the physiological significance of the observed complex as interconnecting site where signaling molecules congregate to execute a coordinated control of membrane excitability.

show abstract

Membrane stretch augments the cardiac muscarinic K+ channel activity

Cited by 28 publications

References 33 publications

Mechanosensitive‐Mediated Interaction, Integration, and Cardiac Control

Mechanosensitive‐Mediated Interaction, Integration, and Cardiac Control

Tertiapin‐Q removes a mechanosensitive component of muscarinic control of the sinoatrial pacemaker in the rat

Coordination of Membrane Excitability through a GIRK1 Signaling Complex in the Atria

Contact Info

Product

Resources

About