Differential inhibition of hjkhj transient outward currents of Kv1.4 and Kv4.3 by endothelin

Hagiwara, Kunie; Nunoki, Kazuo; Ishii, Kuniaki; Abe, Takaaki; Yanagisawa, Teruyuki

doi:10.1016/j.bbrc.2003.09.062

Cited by 21 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The family of neurokinin receptors NK 1 , NK 2 and NK 3 are G-protein coupled receptors which activate phospholipase C (Maggi, 1995(Maggi, ,1997b. The breakdown of phospholipids into diacylglycerol by PLC, activates PKC (Torrens et al, 1997) to phosphorylate and inhibit a number of K + channels (Boland and Jackson, 1999,Hagiwara et al, 2003,Richardson and Vasko, 2002. We have shown that direct activation of PKC with PDBu did not increase firing in DRG neurons.…”

Section: Discussionmentioning

confidence: 82%

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Sculptoreanu

Groat

2007

Experimental Neurology

View full text Add to dashboard Cite

Neurokinins released by capsaicin-responsive (C-R) dorsal root ganglia neurons (DRG) may control firing in these neurons by an autofeedback mechanism. Here we used patch clamp techniques to examine the effects of neurokinins on firing properties of dissociated DRG neurons of male rats. In C-R neurons that generated only a few action potentials (APs, termed phasic) in response to long depolarizing current pulses (600 ms), substance P (SP, 0.5 μM) lowered the AP threshold by 11.0 ±0.3 mV and increased firing from 1.1±0.7 APs to 5.2±0.6 APs. In C-R tonic neurons that fire multiple APs, SP elicited smaller changes in AP threshold (6.0±0.1 mV reduction) and the number of APs (11±1 vs. 9±1 in control). The effects of SP were similar to the effect of heteropodatoxin II (0.05 μM) or low concentrations of 4-aminopyridine (50 μM) that block A-type K + currents. A selective NK 2 agonist, [βAla 8 ]-neurokinin A (4-10) (0.5 μM), mimicked the effects of SP. The effects of SP in C-R phasic neurons were fully reversed by an NK 2 receptor antagonist (MEN10376, 0.5 μM) but only partially by a protein kinase C (PKC) inhibitor (bisindolylmaleimide, 0.5 μM). An NK 3 selective agonist ([MePhe 7 ]-neurokinin B, 0.5 μM), an NK 1 selective agonist ([Sar 9 , Met 11 ]-substance P, 0.5 μM) or activation of PKC with phorbol 12, 13-dibutyrate (0.5 μM) did not change firing. Our data suggest that the excitability of C-R phasic afferent neurons is increased by activation of NK 2 receptors and intracellular signaling mediated only in part by PKC.

show abstract

Section: Discussionmentioning

confidence: 82%

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Sculptoreanu

Groat

2007

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Initially, PKC produces a small increase in the Kv1.4 K ϩ current, which is followed by a more pronounced inhibitory effect (18). Recently, Hagiwara et al (11) demonstrated that endothelin, acting via PKC, causes a strong inhibition of the Kv1.4 channel. In the present study, application of PMA to the neonatal fibroblasts caused a relatively small (ϳ30%) but specific decrease in I to .…”

Section: Expression Of Kv Channels In Neonatal Rat Cardiac Fibroblastsmentioning

confidence: 99%

Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C

Walsh¹,

Zhang²

2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Walsh KB, Zhang J. Neonatal rat cardiac fibroblasts express three types of voltage-gated K ϩ channels: regulation of a transient outward current by protein kinase C. Am J Physiol Heart Circ Physiol 294: H1010-H1017, 2008. First published December 21, 2007 doi:10.1152/ajpheart.01195.2007.-Cardiac fibroblasts regulate myocardial development via mechanical, chemical, and electrical interactions with associated cardiomyocytes. The goal of this study was to identify and characterize voltage-gated K ϩ (Kv) channels in neonatal rat ventricular fibroblasts. With the use of the whole cell arrangement of the patch-clamp technique, three types of voltagegated, outward K ϩ currents were measured in the cultured fibroblasts. The majority of cells expressed a transient outward K ϩ current (Ito) that activated at potentials positive to Ϫ40 mV and partially inactivated during depolarizing voltage steps. Ito was inhibited by the antiarrhythmic agent flecainide (100 M) and BaCl2 (1 mM) but was unaffected by 4-aminopyridine (4-AP; 0.5 and 1 mM). A smaller number of cells expressed one of two types of kinetically distinct, delayed-rectifier K ϩ currents [IK fast (IKf) and IK slow (IKs)] that were strongly blocked by 4-AP. Application of phorbol 12-myristate 13-acetate, to stimulate protein kinase C (PKC), inhibited Ito but had no effect on IKf and IKs. Immunoblot analysis revealed the presence of Kv1.4, Kv1.2, Kv1.5, and Kv2.1 ␣-subunits but not Kv4.2 or Kv1.6 ␣-subunits in the fibroblasts. Finally, pretreatment of the cells with 4-AP inhibited angiotensin II-induced intracellular Ca 2ϩ mobilization. Thus neonatal cardiac fibroblasts express at least three different Kv channels that may contribute to electrical/chemical signaling in these cells. cardiac fibroblasts DEVELOPMENT OF THE VERTEBRATE myocardium requires the interaction of several cell types, including myocytes, fibroblasts, smooth muscle cells, and endothelial cells (2, 3). Although cardiac myocytes make up the bulk of the myocardial volume, the cardiac fibroblast is the most numerous cell type found in the heart and functions in the deposition of the extracellular matrix (2, 3). In addition, fibroblasts can serve as "sentinel cells" that coordinate the myocardial response to chemical and mechanical stimulation through the release of cytokines and growth factors (2,3,15). Release of these signals during myocardial injury may regulate the extent of cardiac hypertrophy and fibrosis during the healing process (5, 15).Recent experiments suggest that cardiac fibroblasts also serve to relay electrical signals in the heart. When plated in primary culture, cardiac fibroblasts form physical interactions with cardiac myocytes through establishment of gap-junctional channels (6,8,14). With the use of a heterocellular culture model, it was established that fibroblasts are capable of relaying electrical excitation over distances as long as 300 m between strands of cardiac myocytes (14). However, the ionic mechanisms responsible for this electrical propagation are not well understoo...

show abstract

“…CaMKII activates the transient outward K + current (I to ) 92–95 and inwardly rectifying (I K1 ) K + current 96 . I to is comprised of I to,fast (K V 4.2/ K V 4.3) and I to,slow (K V 1.4), and site-directed mutagenesis studies have identified K V 4.3 S550 95 and K V 1.4 Thr602 97 as potential phosphorylation targets for CaMKII. Increased CaMKII activity has been shown to slow I to inactivation and accelerate recovery, with an overall effect of shortening the action potential and decreasing the refractory period.…”

Section: Introductionmentioning

confidence: 99%

Calmodulin-Dependent Protein Kinase II: Linking Heart Failure and Arrhythmias

Swaminathan

Purohit

Hund

et al. 2012

Circulation Research

248

232

View full text Add to dashboard Cite

Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the last decade supports a view that activation of the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca2+ or oxidation, upstream signals with the capacity to transition CaMKII into a Ca2+ and calmodulin-independeant, constitutively active enzyme. Constitutively active CaMKII appears poised to participate in disease pathways by catalyzing the phosphorylation of classes of protein targets important for excitation-contraction coupling and cell survival, including ion channels and Ca2+ homeostatic proteins, and transcription factors that drive hypertrophic and inflammatory gene expression. This rich diversity of downstream targets helps to explain the potential for CaMKII to simultaneously affect mechanical and electrical properties of heart muscle cells. Proof of concept studies from a growing number of investigators show that CaMKII inhibition is beneficial for improving myocardial performance and reducing arrhythmias. Here we review the molecular physiology of CaMKII, discuss CaMKII actions at key cellular targets and results of animal models of myocardial hypertrophy, dysfunction and arrhythmias that suggest CaMKII inhibition may benefit myocardial function while reducing arrhythmias.

show abstract

Differential inhibition of hjkhj transient outward currents of Kv1.4 and Kv4.3 by endothelin

Cited by 21 publications

References 35 publications

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C

Calmodulin-Dependent Protein Kinase II: Linking Heart Failure and Arrhythmias

Contact Info

Product

Resources

About

Differential inhibition of hjkhj transient outward currents of Kv1.4 and Kv4.3 by endothelin

Cited by 21 publications

References 35 publications

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C

Calmodulin-Dependent Protein Kinase II: Linking Heart Failure and Arrhythmias

Contact Info

Product

Resources

About

Neonatal rat cardiac fibroblasts express three types of voltage-gated K⁺ channels: regulation of a transient outward current by protein kinase C