scholarly journals Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of KATP Channels or Connexin 43

2019 ◽  
Vol 20 (23) ◽  
pp. 5927 ◽  
Author(s):  
Emiliano Diez ◽  
Jose Sánchez ◽  
Natalia Prado ◽  
Amira Ponce Zumino ◽  
David García-Dorado ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potential ◽  
Connexin 43 ◽  
Electrical Impedance ◽  
Katp Channels ◽  
Antiarrhythmic Effect ◽  
Reperfusion Arrhythmias ◽  
Kinase C ◽  
Action Potential Shortening

Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A1, A2A and A3 receptors, protein kinase C, ATP-dependent potassium (KATP) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A1, A2A and A3 receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a KATP inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.

Activation of Protein Kinase C Increases Neuronal Excitability by Regulating Persistent Na+ Current in Mouse Neocortical Slices

1998 ◽  
Vol 80 (3) ◽  
pp. 1547-1551 ◽  
Author(s):  
Nadav Astman ◽  
Michael J. Gutnick ◽  
Ilya A. Fleidervish
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potential ◽  
Neuronal Excitability ◽  
Specific Protein ◽  
Protein Kinase C Inhibitors ◽  
Cationic Current ◽  
Kinase C ◽  
Layer V ◽  
Neuronal Functions

Astman, Nadav, Michael J. Gutnick, and Ilya A. Fleidervish. Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices. J. Neurophysiol. 80: 1547–1551, 1998. Effects of the protein kinase C activating phorbol ester, phorbol 12-myristate 13-acetate (PMA), were studied in whole cell recordings from layer V neurons in slices of mouse somatosensory neocortex. PMA was applied intracellularly (100 nM to 1 μM) to restrict its action to the cell under study. In current-clamp recordings, it enhanced neuronal excitability by inducing a 10- to 20-mV decrease in voltage threshold for action-potential generation. Because spike threshold in neocortical neurons critically depends on the properties of persistent Na+ current ( I NaP), effects of PMA on this current were studied in voltage clamp. After blocking K+ and Ca2+ currents, I NaP was revealed by applying slow depolarizing voltage ramps from −70 to 0 mV. Intracellular PMA induced a decrease in I NaP at very depolarized membrane potentials. It also shifted activation of I NaP in the hyperpolarizing direction, however, such that there was a significant increase in persistent inward current at potentials more negative than −45 mV. When tetrodotoxin (TTX) was added to the bath, blocking I NaP and leaving only an outward nonspecific cationic current ( I cat), PMA had no apparent effect on responses to voltage ramps. Thus PMA did not affect I cat, and it did not induce any additional current. Intracellular application of the inactive PMA analogue, 4α-PMA, did not affect I NaP. The specific protein kinase C inhibitors, chelerythrine (20 μM) and calphostin C (10 μM), blocked the effect of PMA on I NaP. The data suggest that PMA enhances neuronal excitability via a protein kinase C–mediated increase in I NaP at functionally critical subthreshold voltages. This novel effect would modulate all neuronal functions that are influenced by I NaP, including synaptic integration and active backpropagation of action potential from the soma into the dendrites.

Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary bladder smooth muscle

1993 ◽  
Vol 265 (6) ◽  
pp. C1723-C1728 ◽  
Author(s):  
A. D. Bonev ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Urinary Bladder ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Katp Channels ◽  
Muscle Cells ◽  
Receptor Stimulation ◽  
Kinase C

We explored the possibility that muscarinic receptor stimulation can inhibit ATP-sensitive K+ (KATP) channels in smooth muscle cells from guinea pig urinary bladder. Whole cell K+ currents were measured in smooth muscle cells isolated from the detrusor muscle of the guinea pig bladder. Stimulation of muscarinic receptors by carbachol (CCh; 10 microM) inhibited KATP currents by 60.7%. Guanosine 5'-O-(2-thiodiphosphate) in the pipette (internal) solution prevented the CCh-induced inhibition of KATP currents. Activators of protein kinase C (PKC), a diacylglycerol analogue, and phorbol 12-myristate 13-acetate inhibited KATP currents by 63.5 and 73.9%, respectively. Blockers of PKC (bisindolylmaleimide GF-109203X and calphostin C) greatly reduced CCh inhibition of KATP currents. We propose that muscarinic receptor stimulation inhibits KATP channels in smooth muscle cells from urinary bladder through activation of PKC.

The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

2005 ◽  
Vol 100 (6) ◽  
pp. 1680-1686 ◽  
Author(s):  
Lawrence A. Turner ◽  
Kazuhiro Fujimoto ◽  
Akihiro Suzuki ◽  
Anna Stadnicka ◽  
Zeljko J. Bosnjak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Katp Channels ◽  
Kinase C ◽  
Protein Kinase C Activators

scholarly journals Selectivity of Connexin 43 Channels Is Regulated Through Protein Kinase C–Dependent Phosphorylation

2006 ◽  
Vol 98 (12) ◽  
pp. 1498-1505 ◽  
Author(s):  
Jose F. Ek-Vitorin ◽  
Timothy J. King ◽  
Nathanael S. Heyman ◽  
Paul D. Lampe ◽  
Janis M. Burt
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Connexin 43 ◽  
Kinase C

Modulation of ventricular action potential by alpha 1-adrenoceptors and protein kinase C

1990 ◽  
Vol 258 (3) ◽  
pp. H907-H911 ◽  
Author(s):  
R. T. Dirksen ◽  
S. S. Sheu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Action Potential ◽  
Kinase C ◽  
Adrenoceptor Agonist ◽  
Lower Temperature ◽  
Cardiac Excitation ◽  
Dose Dependent ◽  
Pkc Activation

The effects of the alpha 1-adrenoceptor agonist methoxamine (MTX) and the direct protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBU) on action potentials from guinea pig papillary muscles were studied. Measured with conventional microelectrodes, MTX (1 x 10(-7) to 3 x 10(-4) M) and PDBU (1 x 10(-9) to 1 x 10(-6) M) both caused a dose-dependent and reversible decrease in the action potential duration measured at 90% repolarization (APD90) at 36.5 degrees C. The MTX-mediated response was blocked by both prazosin (3 x 10(-6) M) and phentolamine (1 x 10(-6) M) and mimicked by phenylephrine. Maximal concentrations of the two agents together resulted in only a partial (50%) additive decrease in the APD90. At a lower temperature (27.5 degrees C), PDBU no longer produced a shortening in the APD90 and MTX produced a prolongation in the APD90. These results demonstrate that although alpha 1-adrenoceptor stimulation and PKC activation in guinea pig papillary muscle both lead to a decrease in the APD90, the differences in their effects as related to the magnitude, partial additivity, and temperature dependence suggest that the mechanism of action are not identical. These subtle differences may help to delineate the exact physiological implications of alpha 1-adrenoceptors in cardiac excitation and contraction.

scholarly journals Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells

2007 ◽  
Vol 292 (3) ◽  
pp. H1352-H1363 ◽  
Author(s):  
Lioubov I. Brueggemann ◽  
Christopher J. Moran ◽  
John A. Barakat ◽  
Jay Z. Yeh ◽  
Leanne L. Cribbs ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potential ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Kinase C ◽  
A7r5 Cells ◽  
Dependent Inhibition

[Arg8]-vasopressin (AVP), at low concentrations (10–500 pM), stimulates oscillations in intracellular Ca2+ concentration (Ca2+ spikes) in A7r5 rat aortic smooth muscle cells. Our previous studies provided biochemical evidence that protein kinase C (PKC) activation and phosphorylation of voltage-sensitive K+ (Kv) channels are crucial steps in this process. In the present study, Kv currents ( IKv) and membrane potential were measured using patch clamp techniques. Treatment of A7r5 cells with 100 pM AVP resulted in significant inhibition of IKv. This effect was associated with gradual membrane depolarization, increased membrane resistance, and action potential (AP) generation in the same cells. The AVP-sensitive IKv was resistant to 4-aminopyridine, iberiotoxin, and glibenclamide but was fully inhibited by the selective KCNQ channel blockers linopirdine (10 μM) and XE-991 (10 μM) and enhanced by the KCNQ channel activator flupirtine (10 μM). BaCl2 (100 μM) or linopirdine (5 μM) mimicked the effects of AVP on K+ currents, AP generation, and Ca2+ spiking. Expression of KCNQ5 was detected by RT-PCR in A7r5 cells and freshly isolated rat aortic smooth muscle. RNA interference directed toward KCNQ5 reduced KCNQ5 protein expression and resulted in a significant decrease in IKv in A7r5 cells. IKv was also inhibited in response to the PKC activator 4β-phorbol 12-myristate 13-acetate (10 nM), and the inhibition of IKv by AVP was prevented by the PKC inhibitor calphostin C (250 nM). These results suggest that the stimulation of Ca2+ spiking by physiological concentrations of AVP involves PKC-dependent inhibition of KCNQ5 channels and increased AP firing in A7r5 cells.

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