Amoxapine Inhibits the Delayed Rectifier Outward K+ Current in Mouse Cortical Neurons via cAMP/Protein Kinase A Pathways

2009 ◽  
Vol 332 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Yan-Lin He ◽  
Xiao-Qin Zhan ◽  
Guang Yang ◽  
Ji Sun ◽  
Yan-Ai Mei
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cortical Neurons ◽  
Delayed Rectifier ◽  
K Current ◽  
Kinase A

scholarly journals Effects of protein phosphatase and kinase inhibitors on the cardiac L-type Ca current suggest two sites are phosphorylated by protein kinase A and another protein kinase.

1995 ◽  
Vol 106 (3) ◽  
pp. 393-414 ◽  
Author(s):  
H C Hartzell ◽  
Y Hirayama ◽  
J Petit-Jacques
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Kinase Inhibitors ◽  
Delayed Rectifier ◽  
Internal Perfusion ◽  
Ca Current ◽  
Phosphatase Inhibitors ◽  
Pkc Inhibitors ◽  
Kinase A

We previously showed (Frace, A.M. and H.C. Hartzell. 1993. Journal of Physiology. 472:305-326) that internal perfusion of frog atrial myocytes with the nonselective protein phosphatase inhibitors microcystin or okadaic acid produced an increase in the L-type Ca current (ICa) and a decrease in the delayed rectifier K current (IK). We hypothesized that microcystin revealed the activity of a protein kinase (PKX) that was basally active in the cardiac myocyte that could phosphorylate the Ca and K channels or regulators of the channels. The present studies were aimed at determining the nature of PKX and its phosphorylation target. The effect of internal perfusion with microcystin on ICa or IK was not attenuated by inhibitors of protein kinase A (PKA). However, the effect of microcystin on ICa was largely blocked by the nonselective protein kinase inhibitors staurosporine (10-30 nM), K252a (250 nM), and H-7 (10 microM). Staurosporine and H-7 also decreased the stimulation of ICa by isoproterenol, but K252a was more selective and blocked the ability of microcystin to stimulate ICa without significantly reducing isoproterenol-stimulated current. Internal perfusion with selective inhibitors of protein kinase C (PKC), including the autoinhibitory pseudosubstrate PKC peptide (PKC(19-31)) and a myristoylated derivative of this peptide had no effect. External application of several PKC inhibitors had negative side effects that prevented their use as selective PKC inhibitors. Nevertheless, we conclude that PKX is not PKC. PKA and PKX phosphorylate sites with different sensitivities to the phosphatase inhibitors calyculin A and microcystin. In contrast to the results with ICa, the effect of microcystin on IK was not blocked by any of the kinase inhibitors tested, suggesting that the effect of microcystin on IK may not be mediated by a protein kinase but may be due to a direct effect of microcystin on the IK channel.

scholarly journals Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic β-Cells by Linoleic Acids

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 674-682 ◽  
Author(s):  
Dan Dan Feng ◽  
Ziqiang Luo ◽  
Sang-gun Roh ◽  
Maria Hernandez ◽  
Neveen Tawadros ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Linoleic Acid ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Gated ◽  
K Current ◽  
K Currents ◽  
Kinase A

Free fatty acids (FFAs), in addition to glucose, have been shown to stimulate insulin release through the G protein-coupled receptor (GPCR)40 receptor in pancreatic β-cells. Intracellular free calcium concentration ([Ca2+]i) in β-cells is elevated by FFAs, although the mechanism underlying the [Ca2+]i increase is still unknown. In this study, we investigated the action of linoleic acid on voltage-gated K+ currents. Nystatin-perforated recordings were performed on identified rat β-cells. In the presence of nifedipine, tetrodotoxin, and tolbutamide, voltage-gated K+ currents were observed. The transient current represents less than 5%, whereas the delayed rectifier current comprises more than 95%, of the total K+ currents. A long-chain unsaturated FFA, linoleic acid (10 μm), reversibly decreased the amplitude of K+ currents (to less than 10%). This reduction was abolished by the cAMP/protein kinase A system inhibitors H89 (1 μm) and Rp-cAMP (10 μm) but was not affected by protein kinase C inhibitor. In addition, forskolin and 8′-bromo-cAMP induced a similar reduction in the K+ current as that evoked by linoleic acid. Insulin secretion and cAMP accumulation in β-cells were also increased by linoleic acid. Methyl linoleate, which has a similar structure to linoleic acid but no binding affinity to GPR40, did not change K+ currents. Treatment of cultured cells with GPR40-specific small interfering RNA significantly reduced the decrease in K+ current induced by linoleic acid, whereas the cAMP-induced reduction of K+ current was not affected. We conclude that linoleic acid reduces the voltage-gated K+ current in rat β-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca2+]i and insulin secretion.

scholarly journals Ethanol Activation of Protein Kinase A Regulates GABAAα1 Receptor Function and Trafficking in Cultured Cerebral Cortical Neurons

2013 ◽  
Vol 345 (2) ◽  
pp. 317-325 ◽  
Author(s):  
Stephen L. Carlson ◽  
Sandeep Kumar ◽  
David F. Werner ◽  
Christopher E. Comerford ◽  
A. Leslie Morrow
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cortical Neurons ◽  
Receptor Function ◽  
Cerebral Cortical Neurons ◽  
Kinase A
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