ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K<sup>+</sup>Currents

Hu, Huijuan; Glauner, Kathi S.; Gereau, Robert W.

doi:10.1152/jn.00340.2003

Cited by 138 publications

(128 citation statements)

References 32 publications

(36 reference statements)

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“…It is interesting to note that blockade of the basal steady-state activity of MAPKs or PI3K produced partial inhibition of the channels (I K or I K1 ), favoring a model where basal constitutive (i.e., IGF-I-independent) MAPKs and PI3K may work independently to sustain the fundamental activity of the channel (2). These data are in agreement with recent studies (1,2,25,58,61) showing direct basal regulation of repolarizing potassium channel activities by MAPK. In that regard, cardiac hypertrophy was associated with MAPK-dependent deregulation of I K and I to (58).…”

Section: Basal Regulation Of Potassium Channels By Mapk and Pi3ksupporting

confidence: 87%

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Teos¹,

Zhao²,

Alvin³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The potassium channels IK and IK1, responsible for the action potential repolarization and resting potential respectively, are altered during cardiac hypertrophy. The activation of insulin-like growth factor-I (IGF-I) during hypertrophy may affect channel activity. The aim was to examine the modulatory effects of IGF-I on IK and IK1 through mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways during hypertrophy. With the use of specific inhibitors for ERK1/2 (PD98059), p38 MAPK (SB203580) and PI3K/Akt (LY294002), Western blot and whole cell patch-clamp were conducted on sham and aorto-caval shunt-induced hypertrophy adult rat myocytes. Basal activation levels of MAPKs and Akt were increased during hypertrophy. Acute IGF-I (10 Ϫ8 M) enhanced basal activation levels of these kinases in normal hearts but only those of Akt in hypertrophied ones. IK and IK1 activities were lowered by IGF-I. Inhibition of ERK1/2, p38 MAPK, or Akt reduced basal IK activity by 70, 32, or 50%, respectively, in normal cardiomyocytes vs. 53, 34, or 52% in hypertrophied ones. However, basal activity of IK1 was reduced by 45, 48, or 45% in the former vs. 63, 43, or 24% in the latter. The inhibition of either MAPKs or Akt alleviated IGF-I effects on IK and IK1. We conclude that basal IK and IK1 are positively maintained by steady-state Akt and ERK activities.

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Section: Basal Regulation Of Potassium Channels By Mapk and Pi3ksupporting

confidence: 87%

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Teos¹,

Zhao²,

Alvin³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…For example, in hepatocytes the basal activity of p38 MAP kinase is required for maintenance of cell volume through tonic inhibition of Na ϩ -permeable ion channels (30). In dendrites of pyramidal neurons, the basal activity of ERK1/2 is responsible for sustained downregulation of A-type outward potassium currents (31,32).…”

Section: Discussionmentioning

confidence: 99%

ERK1/2 Controls Na,K-ATPase Activity and Transepithelial Sodium Transport in the Principal Cell of the Cortical Collecting Duct of the Mouse Kidney

Michlig

Mercier

Doucet

et al. 2004

Journal of Biological Chemistry

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The collecting duct of normal kidney exhibits significant activity of the MEK1/2-ERK1/2 pathway as shown in vivo by immunostaining of phosphorylated active ERK1/2 (pERK1/2). The MEK1/2-ERK1/2 pathway controls many different ion transports both in proximal and distal nephron, raising the question of whether this pathway is involved in the basal and/or hormone-dependent transepithelial sodium reabsorption in the principal cell of the cortical collecting duct (CCD), a process mediated by the apical epithelial sodium channel and the basolateral sodium pump (Na,K-ATPase). To answer this question we used ex vivo microdissected CCDs from normal mouse kidney or in vitro cultured mpkCCD cl4 principal cells. Significant basal levels of pERK1/2 were observed ex vivo and in vitro. Aldosterone and vasopressin, known to up-regulate sodium reabsorption in CCDs, did not change ERK1/2 activity either ex vivo or in vitro. Basal and aldosterone-or vasopressin-stimulated sodium transport was down-regulated by the MEK1/2 inhibitor PD98059, in parallel with a decrease in pERK1/2 in vitro. The activity of Na,K-ATPase but not that of epithelial sodium channel was inhibited by MEK1/2 inhibitors in both unstimulated and aldosterone-or vasopressin-stimulated CCDs in vitro. Cell surface biotinylation showed that intrinsic activity rather than cell surface expression of Na,K-ATPase was controlled by pERK1/2. PD98059 also significantly inhibited the activity of Na,K-ATPase ex vivo. Our data demonstrate that the ERK1/2 pathway controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell and indicate that basal constitutive activity of the ERK1/2 pathway is a critical component of this control.The extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) 1 pathway, also known as p42 and p44 mitogen-activated protein (MAP) kinase pathway, plays a critical role in cellular responses to a wide variety of external stimuli including hormones, growth factors, and environmental stress (for review, see Refs. 1 and 2). The ERK1/2 pathway is a three-step kinase cascade in which ERK1/2 kinases are phosphorylated/ activated by two immediate upstream MAP kinases (MEK1 and MEK2 (MEK1/2)) that are in turn phosphorylated/activated by several MAP kinases (i.e. MOS, C-Raf, and B-Raf). Activated ERK1/2 (pERK1/2) phosphorylates various downstream effectors involved in differentiation, proliferation, apoptosis, survival, cellular metabolism, and ion transport. The MAP kinase cascade may also be constitutively activated independent of external stimuli or ligands. This basal activity is the result of the balance between positive and negative factors regulating MAP kinases activity; that is, phosphatases, subcellular localization, expression of scaffold proteins, and activity of other kinases. In the kidney, the ERK1/2 pathway is involved in the hormonal regulation of different apical and basolateral channels or transporters expressed along the nephron for maintaining the extracellular fluid homeostasis. In the proximal tubule the ERK...

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“…Although it is possible for pERK1/2 to modulate ion channel activity directly (Hu et al, 2003), the scaffolding and guiding roles of F-actin in ERK1/2 activation provide an optimal condition for direct interactions between pERK1/2 and the electrogenic organelles in OT neuronal membranes. Possibly, the negative influence of disturbing F-actin dynamics on burst generation is related to dissociation of newly activated ERK1/2 from F-actin.…”

Section: Actin Reorganization and Ot-evoked Burstsmentioning

confidence: 99%

Interaction of Extracellular Signal-Regulated Protein Kinase 1/2 with Actin Cytoskeleton in Supraoptic Oxytocin Neurons and Astrocytes: Role in Burst Firing

Wang¹,

Hatton²

2007

J. Neurosci.

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Neuronal firing patterns determine the manner of neurosecretion, the underlying mechanisms of which are poorly understood. Using supraoptic nuclei in brain slices from lactating rats, we examined the involvement of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and filamentous actin (F-actin) in burst generation by oxytocin (OT) neurons. Blocking phosphorylation of ERK1/2 (pERK1/2) decreased miniature EPSCs and blocked OT-evoked bursts, as did intracellularly loading an antibody against pERK1/2. OT (10 pM) increased cytosolic pERK1/2 close to the cell membrane within the first 5 min, subsiding by 30 min, whereas OT elicited pERK1/2 nuclear translocation in closely associated supraoptic astrocytes. The increased pERK1/2 was tightly correlated with spatiotemporal actin dynamics. In OT neurons, OT initially increased F-actin, particularly at membrane subcortical areas, and then decreased it after 30 min. Both polymerization and depolymerization of actin cytoskeleton were associated with bursts, but only polymerization facilitated OTevoked bursts. Blocking ERK1/2 activation blocked OT-evoked actin polymerization, whereas depolymerizing F-actin increased pERK1/2 expression. These changes were further identified in vivo. In intact animals, suckling increased ERK1/2 activation in the cytosol and membrane subcortical area F-actin formation in OT neurons, whereas it increased F-actin concentration in astrocytic somata. Coimmunoprecipitation showed that suckling increased molecular interactions between pERK1/2 and actin. Finally, two different blockers of ERK1/2 kinase injected intracerebroventricularly reduced suckling-evoked milk ejections. This is the first demonstration that OT mediation of suckling-evoked bursts/milk ejections is via interactions between pERK1/2 and actin cytoskeleton.

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ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K⁺Currents

Cited by 138 publications

References 32 publications

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

ERK1/2 Controls Na,K-ATPase Activity and Transepithelial Sodium Transport in the Principal Cell of the Cortical Collecting Duct of the Mouse Kidney

Interaction of Extracellular Signal-Regulated Protein Kinase 1/2 with Actin Cytoskeleton in Supraoptic Oxytocin Neurons and Astrocytes: Role in Burst Firing

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ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K+Currents

Cited by 138 publications

References 32 publications

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

ERK1/2 Controls Na,K-ATPase Activity and Transepithelial Sodium Transport in the Principal Cell of the Cortical Collecting Duct of the Mouse Kidney

Interaction of Extracellular Signal-Regulated Protein Kinase 1/2 with Actin Cytoskeleton in Supraoptic Oxytocin Neurons and Astrocytes: Role in Burst Firing

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ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K⁺Currents