scholarly journals Neuromedin S Increases L-type Ca2+Channel Currents Through Gia-protein and Phospholipase C-dependent Novel Protein Kinase C Delta Pathway in Adult Rat Ventricular Myocytes

2012 ◽  
Vol 30 (3) ◽  
pp. 618-630 ◽  
Author(s):  
Run-Xiang Chen ◽  
Feng Liu ◽  
Yong Li ◽  
Guang-An Liu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Ventricular Myocytes ◽  
Protein Kinase C Delta ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Kinase C ◽  
Channel Currents ◽  
Novel Protein

scholarly journals Growth Hormone Secretagogues Reduce Transient Outward K+ Current via Phospholipase C/Protein Kinase C Signaling Pathway in Rat Ventricular Myocytes

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1228-1235 ◽  
Author(s):  
Qiang Sun ◽  
Wei-Jin Zang ◽  
Chen Chen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potential ◽  
Phospholipase C ◽  
Action Potential Duration ◽  
Ventricular Myocytes ◽  
Signaling Cascade ◽  
Dependent Manner ◽  
Rat Ventricular Myocytes ◽  
Kinase C

Endogenous ghrelin and its synthetic counterpart hexarelin are peptide GH secretagogues (GHS) that exert a positive ionotropic effect in the cardiovascular system. The mechanism by which GHS modulate cardiac electrophysiology properties to alter myocyte contraction is poorly understood. In the present study, we examined whether GHS regulates the transient outward potassium current (Ito) as well as the putative intracellular signaling cascade responsible for such regulation. GHS and experimental agents were applied locally onto freshly isolated adult Sprague-Dawley rat ventricular myocytes and action potential morphology and Ito was recorded using nystatin-perforated whole-cell patch-clamp recording technique. Under current clamp, ghrelin and hexarelin (10 nm) significantly prolonged action potential duration. Under voltage clamp, hexarelin and ghrelin inhibited Ito in a concentration-dependent manner. This inhibition was abolished in the presence of the GHS receptor (GHS-R) antagonist [d-Lys3]GH-releasing peptide-6 (10 μm) and GHS-R1a-specific antagonist BIM28163 (1 μm). GHS-induced Ito inhibition was totally reversed by the phospholipase C inhibitor U73122 (5 μm) and protein kinase C inhibitors GÖ6983 (1 μm) and calphostin C (0.1 μm) but not by the cAMP antagonist Rp-cAMP (100 μm) or the PKA inhibitor H89 (1 μm). We conclude that hexarelin and ghrelin activate phospholipase C and protein kinase C signaling cascade through the stimulation of the GHS-R, resulting in a decrease in the Ito current and subsequent prolongation of action potential duration.

Propofol Increases Myofilament Ca2+Sensitivity and Intracellular pH via  Activation of Na+–H+Exchange in Rat Ventricular Myocytes

2001 ◽  
Vol 94 (6) ◽  
pp. 1096-1104 ◽  
Author(s):  
Noriaki Kanaya ◽  
Paul A. Murray ◽  
Derek S. Damron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Ph ◽  
Ventricular Myocytes ◽  
Intracellular Acidosis ◽  
Solution Ph ◽  
Rat Ventricular Myocytes ◽  
Actomyosin Atpase ◽  
Adult Rat ◽  
Kinase C

Background The objectives were to determine the extent and mechanism of action by which propofol increases myofilament Ca2+ sensitivity and intracellular pH (pHi) in ventricular myocytes. Methods Freshly isolated adult rat ventricular myocytes were used for the study. Cardiac myofibrils were extracted for assessment of myofibrillar actomyosin adenosine triphosphatase (ATPase) activity. Myocyte shortening (video edge detection) and pHi (2',7'-bis-(2-carboxyethyl)-5(6')-carboxyfluorescein, 500/440 ratio) were monitored simultaneously in individual cells field-stimulated (0.3 Hz) and superfused with HEPES-buffered solution (pH 7.4, 30 degrees C). Results Propofol (100 microM) reduced the Ca2+ concentration required for activation of myofibrillar actomyosin ATPase from pCa 5.7 +/- 0.01 to 6.6 +/- 0.01. Increasing pHi (7.05 +/- 0.03 to 7.39 +/- 0.04) with NH4Cl increased myocyte shortening by 35 +/- 12%. Washout of NH4Cl decreased pHi to 6.82 +/- 0.03 and decreased myocyte shortening to 52 +/- 10% of control. Propofol caused a dose-dependent increase in pHi but reduced myocyte shortening. The propofol-induced increase in pHi was attenuated, whereas the decrease in myocyte shortening was enhanced after pretreatment with ethylisopropyl amiloride, a Na+-H+ exchange inhibitor, or bisindolylmaleimide I, a protein kinase C inhibitor. Propofol also attenuated the NH4Cl-induced intracellular acidosis, increased the rate of recovery from acidosis, and attenuated the associated decrease in myocyte shortening. Propofol caused a leftward shift in the extracellular Ca2+-shortening relation, and this effect was attenuated by ethylisopropyl amiloride. Conclusions These results suggest that propofol increases the sensitivity of myofibrillar actomyosin ATPase to Ca2+ (ie., increases myofilament Ca2+ sensitivity), at least in part by increasing pHi via protein kinase C-dependent activation of Na+-H+ exchange.

1,2-Dioctanoyl-sn-glycerol depresses cardiac L-type Ca2+ current: independent of protein kinase C activation

1996 ◽  
Vol 270 (2) ◽  
pp. C655-C662 ◽  
Author(s):  
K. D. Schreur ◽  
S. Liu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ventricular Myocytes ◽  
Inhibitory Effect ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Kinase C ◽  
Whole Cell Patch Clamp ◽  
Steady State Inactivation ◽  
Slope Factor

The present study examines the effect of 1,2-dioctanoyl-sn-glycerol (DiC8), a diacylglycerol analogue, on L-type Ca2+ current (ICa,L) in adult rat ventricular myocytes using whole cell patch-clamp techniques. Extracellular application of DiC8 (1-10 microM) resulted in a concentration-dependent inhibition of peak ICa,L (half-maximum inhibitory concentration = 2.2 microM). Results obtained from the current-voltage relationship showed that DiC8 decreased the slope conductance. In addition, DiC8 increased the rate of Ba2+ current inactivation and caused a hyperpolarizing shift in the steady-state inactivation by 6 mV and a decrease in the slope factor. The DiC8-induced inhibition of ICa,L was neither mimicked by activation of protein kinase C (PKC) with 100 nM phorbol 12-myristate 13-acetate (PMA) no prevented by inhibition of PKC with 30 microM H-7, 100 nM staurosporine, or 24-h pretreatment with PMA. These results suggest that in rat ventricular myocytes 1) 1,2-sn-diacylglycerol (DAG) inhibits ICa,L, possibly by facilitating channel inactivation and decreasing channel availability and 2) this inhibitory effect of DAG is independent of PKC activation.

Protein kinase C-ζ modulates thromboxane A2-mediated apoptosis in adult ventricular myocytes via Akt

2002 ◽  
Vol 282 (1) ◽  
pp. H320-H327 ◽  
Author(s):  
Yukitaka Shizukuda ◽  
Peter M. Buttrick
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Kinase Assay ◽  
Dependent Manner ◽  
Adult Rat ◽  
Kinase C ◽  
Adult Cardiac Myocytes ◽  
Pkc Ζ

We hypothesized that thromboxane A2 (TxA2) receptor stimulation directly induces apoptosis in adult cardiac myocytes. To investigate this, we exposed cultured adult rat ventricular myocytes (ARVM) to a TxA2 mimetic [1S-[1α,2α(Z),3β(1E,3S*),4α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) for 24 h. Stimulation with I-BOP induced apoptosis in a dose-dependent manner and was completely prevented by a TxA2 receptor antagonist, SQ-29548. We further investigated the role of protein kinase C (PKC) in this process. TxA2 stimulation resulted in membrane translocation of PKC-ζ but not PKC-α, -βII, -δ, and -ε at 3 min and 1 h. The activation of PKC-ζ by I-BOP was confirmed using an immune complex kinase assay. Treatment of ARVM with a cell-permeable PKC-ζ pseudosubstrate peptide (ζ-PS) significantly attenuated apoptosis by I-BOP. In addition, I-BOP treatment decreased baseline Akt activity and its decrease was reversed by treatment with ζ-PS. The inhibition of phosphatidylinositol 3-kinase upstream of Akt by wortmannin or LY-294002 abolished the antiapoptotic effect of ζ-PS. Therefore, our results suggest that the activation of PKC-ζ modulates TxA2 receptor-mediated apoptosis at least, in part, through Akt activity in adult cardiac myocytes.

Arachidonic acid enhances contraction and intracellular Ca2+ transients in individual rat ventricular myocytes

1997 ◽  
Vol 272 (1) ◽  
pp. H350-H359 ◽  
Author(s):  
D. S. Damron ◽  
B. A. Summers
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cardiac Muscle ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Receptor Activation ◽  
K Channels ◽  
Rat Ventricular Myocytes ◽  
Kinase C

Modulation of intracellular free Ca2+ concentration ([Ca2+]i) by inotropic stimuli alters contractility in cardiac muscle. Arachidonic acid (AA), a precursor for eicosanoid formation, is released in response to receptor activation and myocardial ischemia and has been demonstrated to alter K+ and Ca2+ channel activity. We investigated the effects of AA on contractility by simultaneously measuring [Ca2+]i and shortening in single field-stimulated rat ventricular myocytes. [Ca2+]i transients were measured using fura 2, and myocyte shortening was assessed using video edge detection. AA stimulated a doubling in the amplitude of the [Ca2+]i transient and a twofold increase in myocyte shortening. In addition, AA stimulated a 30% increase in the time to 50% diastolic [Ca2+]i and a 35% increase in the time to 50% relengthening. These effects of AA were mediated by AA itself (56 +/- 5%) and by cyclooxygenase metabolites. Pretreatment with the protein kinase C inhibitors staurosporine and chelerythrine nearly abolished (> 90% inhibition) these AA-induced effects. Inhibition of voltagegated K+ channels with 4-aminopyridine mimicked the effects of AA. Addition of AA to the 4-aminopyridine-treated myocyte had no additional effect on parameters of contractile function. These data indicate that AA alters the amplitude and duration of Ca2- transients and myocyte shortening via protein kinase C-dependent inhibition of voltage-gated K+ channels. Release of AA by phospholipases in response to receptor activation by endogenous mediators or pathological stimuli may be involved in mediating inotropic responses in cardiac muscle.

Enhancement of contraction and L-type Ca2+ current by murrayafoline-A via protein kinase C in rat ventricular myocytes

2016 ◽  
Vol 784 ◽  
pp. 33-41
Author(s):  
Bojjibabu Chidipi ◽  
Min-Jeong Son ◽  
Joon-Chul Kim ◽  
Jeong Hyun Lee ◽  
Tran Quoc Toan ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ventricular Myocytes ◽  
Rat Ventricular Myocytes ◽  
Kinase C
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