The Role of Gi-proteins andβ-Adrenoceptors in the Age-related Decline of Contraction in Guinea-pig Ventricular Myocytes

1997 ◽  
Vol 29 (2) ◽  
pp. 439-448 ◽  
Author(s):  
Nicola Ferrara ◽  
Michael Bö ◽  
Oliver Zolk ◽  
Peter O»Gara ◽  
Sian E. Harding
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Age Related ◽  
Gi Proteins

Antisense inhibition of Na+/Ca2+ exchange during anoxia/reoxygenation in ventricular myocytes

2001 ◽  
Vol 281 (5) ◽  
pp. H2184-H2190 ◽  
Author(s):  
B. N. Eigel ◽  
R. W. Hadley
Keyword(s):  
Guinea Pig ◽  
Antisense Oligonucleotide ◽  
Ventricular Myocytes ◽  
Antisense Inhibition ◽  
Start Site ◽  
Intracellular Ca

This study investigated the role of the Na+/Ca2+ exchanger (NCX) in regulating cytosolic intracellular Ca2+concentration ([Ca2+]i) during anoxia/reoxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+]i overload in this model was tested through inhibition of NCX expression by an antisense oligonucleotide. Immunocytochemistry revealed that this antisense oligonucleotide, directed at the area around the start site of the guinea pig NCX1, specifically reduced NCX expression in cultured adult myocytes by 90 ± 4%. Antisense treatment inhibited evoked NCX activity by 94 ± 3% and decreased the rise in [Ca2+]i during anoxia/reoxygenation by 95 ± 3%. These data suggest that NCX is the predominant mechanism mediating Ca2+ overload during anoxia/reoxygenation in guinea-pig ventricular myocytes.

scholarly journals On the mechanism of rectification of the isoproterenol-activated chloride current in guinea-pig ventricular myocytes.

1993 ◽  
Vol 102 (5) ◽  
pp. 871-895 ◽  
Author(s):  
J L Overholt ◽  
M E Hobert ◽  
R D Harvey
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Rate Theory ◽  
Constant Field ◽  
Patch Clamp Technique ◽  
Site Model ◽  
Outward Rectification ◽  
Current Equation

The whole cell configuration of the patch clamp technique was used to investigate the mechanism underlying rectification of the isoproterenol-activated chloride (Cl-) current in isolated guinea pig ventricular myocytes. When extracellular Cl- was replaced with either bromide (Br-), glutamate (Glut), iodide (I-), isethionate (Iseth), or nitrate (NO3-), the magnitude of the shift in reversal potential of the macroscopic current suggested the following selectivity sequence: NO3- > Br- > or = Cl- > or = I- > Iseth > or = Glut. This information was used to investigate the role of permeant ions in rectification of this current. Consistent with previous observations, when the concentration of intracellular Cl- (Cli-) was less than the concentration of extracellular Cl- (Clo-) (40 mM Cli-/150 mM Clo-) the current exhibited outward rectification, but when Cli- was increased to equal that outside (150 Cli-/150 Clo-), the current no longer rectified. Rectification in the presence of asymmetrical concentrations of permeant ions on either side of the membrane is predicted by constant field theory, as described by the Goldman-Hodgkin-Katz current equation. However, when the Cl- gradient was reversed (150 Cli-/40 Clo-) the current did not rectify in the opposite direction, and in the presence of lower symmetrical concentrations of Cl- inside and out (40 Cli-/40 Clo-), outward rectification did not disappear. Reducing Cli- by equimolar replacement with glutamate caused a concentration dependent increase in the degree of rectification. However, when Cli- was replaced with more permeant anions (NO3- and Br-), rectification was not observed. These results can be explained by a single binding site model based on Eyring rate theory, indicating that rectification is a function of the concentration and the permeability of the anions in the intracellular solution.

Role of protein kinase C in α1-adrenergic regulation of aNa i in guinea pig ventricular myocytes

2000 ◽  
Vol 279 (4) ◽  
pp. H1661-H1668 ◽  
Author(s):  
Su-Hyun Jo ◽  
Chung-Hyun Cho ◽  
Soo Wan Chae ◽  
Chin O. Lee
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Receptor Activation ◽  
Adrenergic Regulation ◽  
Kinase C ◽  
Gf 109203X ◽  
Stimulation Of

We investigated the role of protein kinase C (PKC) in α1-adrenergic regulation of intracellular Na+activity (aNa i) in single guinea pig ventricular myocytes. aNa i and membrane potentials were measured with the Na+-sensitive indicator sodium-binding benzofuran isophthalate and conventional microelectrodes, respectively, at room temperature (24–26°C) while myocytes were stimulated at a rate of 0.25–0.3 Hz. The PKC activator 4β-phorbol 12-myristate 13-acetate (PMA) decreased aNa i in a concentration-dependent manner. PMA (100 nM) produced a maximal decrease in aNa i of 1.5 mM from 6.5 ± 0.4 to 5.0 ± 0.4 mM (means ± SE, n = 12, P< 0.01). The PMA concentration required for a half-maximal decrease in aNa i was 0.46 ± 0.13 nM ( n = 3, P < 0.01). An inactive phorbol, 4α-phorbol 12-myristate 13-acetate, did not decrease aNa i. The decrease caused by PMA could be blocked by the PKC inhibitors staurosporine and bisindolylmaleimide I (GF-109203X). Stimulation of the α1-adrenoceptor with 50 μM phenylephrine decreased aNa i from 6.1 ± 0.3 to 4.6 ± 0.3 mM ( n = 11, P< 0.01). The decrease in aNa i produced by phenylephrine was blocked by pretreatment with staurosporine, GF-109203X, or PMA. The decrease in aNa i produced by PMA was not prevented by pretreatment with tetrodotoxin but was blocked by pretreatment with strophanthidin or high extracellular K+ concentration. The results suggest that α1-adrenergic receptor activation results in a decrease in aNa i via PKC-induced stimulation of the Na+-K+ pump in cardiac myocytes.

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