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

2008 ◽  
Vol 294 (2) ◽  
pp. H1010-H1017 ◽  
Author(s):  
Kenneth B. Walsh ◽  
Jining Zhang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cardiac Fibroblasts ◽  
Neonatal Rat ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Kv Channels ◽  
Kinase C ◽  
Α Subunits

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+ (Kv) channels in neonatal rat ventricular fibroblasts. With the use of the whole cell arrangement of the patch-clamp technique, three types of voltage-gated, outward K+ currents were measured in the cultured fibroblasts. The majority of cells expressed a transient outward K+ current ( Ito) that activated at potentials positive to −40 mV and partially inactivated during depolarizing voltage steps. Ito was inhibited by the antiarrhythmic agent flecainide (100 μM) 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+ 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 α-subunits but not Kv4.2 or Kv1.6 α-subunits in the fibroblasts. Finally, pretreatment of the cells with 4-AP inhibited angiotensin II-induced intracellular Ca2+ mobilization. Thus neonatal cardiac fibroblasts express at least three different Kv channels that may contribute to electrical/chemical signaling in these cells.

scholarly journals Arginine Vasopressin Potentiates the Stimulatory Action of CRH on Pituitary Corticotropes via a Protein Kinase C–Dependent Reduction of the Background TREK-1 Current

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3661-3672 ◽  
Author(s):  
Andy K. Lee ◽  
Frederick W. Tse ◽  
Amy Tse
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Arginine Vasopressin ◽  
Underlying Mechanism ◽  
Sk Channels ◽  
Acth Secretion ◽  
Patch Clamp Technique ◽  
Stimulatory Action ◽  
Kinase C ◽  
Perforated Patch Clamp

The hypothalamic hormone arginine vasopressin (AVP) potentiates the stimulatory action of CRH on ACTH secretion from pituitary corticotropes, but the underlying mechanism is elusive. Using the perforated patch-clamp technique to monitor membrane potentials in mouse corticotropes, we found that AVP triggered a transient hyperpolarization that was followed by a sustained depolarization. The hyperpolarization was caused by intracellular Ca2+ release that in turn activated the small conductance Ca2+-activated K+ (SK) channels. The depolarization was due to the suppression of background TWIK-related K+ (TREK)-1 channels. Direct activation of protein kinase C (PKC) reduced the TREK-1 current, whereas PKC inhibition attenuated the AVP-mediated reduction of the TREK-1 current, implicating the involvement of PKC. The addition of CRH (which stimulates the protein kinase A pathway) in the presence of AVP, or vice versa, resulted in further suppression of the TREK-1 current. In corticotropes with buffered cytosolic Ca2+ concentration ([Ca2+]i), AVP evoked a sustained depolarization, and the coapplication of AVP and CRH caused a larger depolarization than that evoked by AVP or CRH alone. In cells with minimal perturbation of [Ca2+]i and background TREK-1 channels, CRH evoked a sustained depolarization that was superimposed with action potentials, and the subsequent coapplication of AVP and CRH triggered a transient hyperpolarization that was followed by a larger depolarization. In summary, AVP and CRH have additive effects on the suppression of the TREK-1 current, resulting in a more robust depolarization in corticotropes. We suggest that this mechanism contributes to the potentiating action of AVP on CRH-evoked ACTH secretion.

scholarly journals Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation

1999 ◽  
Vol 277 (3) ◽  
pp. L558-L565 ◽  
Author(s):  
Scott A. Barman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Channel Blocker ◽  
Pressor Response ◽  
Vascular Occlusion ◽  
Membrane Depolarization ◽  
Delayed Rectifier ◽  
Vascular Compliance ◽  
Kinase C ◽  
Pkc Activation

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10−7 M) and thymeleatoxin (THX; 10−7 M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10−5 M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10−4 M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10−5 M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

ANG II-mediated inhibition of neuronal delayed rectifier K+ current: role of protein kinase C-α

2001 ◽  
Vol 281 (1) ◽  
pp. C17-C23 ◽  
Author(s):  
Sheng-Jun Pan ◽  
Mingyan Zhu ◽  
Mohan K. Raizada ◽  
Colin Sumners ◽  
Craig H. Gelband
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Ang Ii ◽  
Mediated Effects ◽  
Kinase C ◽  
K Current ◽  
Pkc Isozymes

It was previously determined that ANG II and phorbol esters inhibit Kv current in neurons cultured from newborn rat hypothalamus and brain stem in a protein kinase C (PKC)- and Ca2+-dependent manner. Here, we have further defined this signaling pathway by investigating the roles of “physiological” activators of PKC and different PKC isozymes. The cell-permeable PKC activators, diacylglycerol (DAG) analogs 1,2-dioctanoyl- sn-glycerol (1 μmol/l, n = 7) and 1-oleoyl-2-acetyl- sn-glycerol (1 μmol/l, n = 6), mimicked the effect of ANG II and inhibited Kv current. These effects were abolished by the PKC inhibitor chelerythrine (1 μmol/l, n = 5) or by chelation of internal Ca2+ ( n = 8). PKC antisense (AS) oligodeoxynucleotides (2 μmol/l) against Ca2+-dependent PKC isoforms were applied to the neurons to manipulate the endogenous levels of PKC. PKC-α-AS ( n = 4) treatment abolished the inhibitory effects of ANG II and 1-oleoyl-2-acetyl- sn-glycerol on Kv current, whereas PKC-β-AS ( n = 4) and PKC-γ-AS ( n = 4) did not. These results suggest that the angiotensin type 1 receptor-mediated effects of ANG II on neuronal Kv current involve activation of PKC-α.

Orexin-B Augments Voltage-Gated L-Type Ca2+ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes

2003 ◽  
Vol 77 (3) ◽  
pp. 141-152 ◽  
Author(s):  
Ruwei Xu ◽  
Sang-Gun Roh ◽  
Changhong Gong ◽  
Maria Hernandez ◽  
Yoichi Ueta ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signalling Pathway ◽  
Voltage Gated ◽  
Kinase C

Subnanomolar concentration of VIP induces the nuclear translocation of protein kinase C in neonatal rat cortical astrocytes

1994 ◽  
Vol 39 (4) ◽  
pp. 355-363 ◽  
Author(s):  
Z. Oláh ◽  
Cs. Lehel ◽  
W. B. Anderson ◽  
D. E. Brenneman ◽  
D. v. Agoston
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Neonatal Rat ◽  
Kinase C ◽  
Cortical Astrocytes
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