The inhibitory effect of β-stimulation on the Na/K pump current in guinea pig ventricular myocytes is mediated by a cAMP-dependent PKA pathway

1998 ◽  
Vol 435 (4) ◽  
pp. 479-484 ◽  
Author(s):  
J. Gao ◽  
I. S. Cohen ◽  
R. T. Mathias ◽  
G. J. Baldo
1989 ◽  
Vol 64 (6) ◽  
pp. 1063-1069 ◽  
Author(s):  
D J Mogul ◽  
H H Rasmussen ◽  
D H Singer ◽  
R E Ten Eick

2002 ◽  
Vol 136 (3) ◽  
pp. 361-366 ◽  
Author(s):  
Yasuhide Watanabe ◽  
Takahiro Iwamoto ◽  
Munekazu Shigekawa ◽  
Junko Kimura

2012 ◽  
Vol 120 (1) ◽  
pp. 59-62 ◽  
Author(s):  
Tomomi Yamakawa ◽  
Yasuhide Watanabe ◽  
Hiroshi Watanabe ◽  
Junko Kimura

2001 ◽  
Vol 132 (6) ◽  
pp. 1317-1325 ◽  
Author(s):  
Yasuhide Watanabe ◽  
Takahiro Iwamoto ◽  
Isao Matsuoka ◽  
Satoko Ohkubo ◽  
Tomoyuki Ono ◽  
...  

1995 ◽  
Vol 268 (3) ◽  
pp. H1027-H1036 ◽  
Author(s):  
J. B. Shen ◽  
A. J. Pappano

We previously showed that palmitoyl-L-carnitine (L-PC) inhibits the Na/K pump current (INa/K). In the present report, we test the hypothesis that L-PC, like ouabain, should increase myocyte shortening. Membrane potentials or ionic currents were recorded simultaneously with cell shortening in single guinea pig ventricular myocytes at room temperature (22 degrees C). Like ouabain, L-PC (1 microM) reversibly depolarized the resting membrane, decreased action potential duration, and increased the amplitude of myocyte contractions. Neither L-PC nor ouabain had a significant effect on Ca current (ICa). When L-PC increased cell shortening during ramp voltage clamp, membrane current shifted inward at voltages negative to -20 mV and shifted outward at more positive voltages. Similar to toxic concentrations of ouabain, L-PC induced transient inward currents and aftercontractions. At concentrations that inhibit INa/K, L-PC acted like ouabain to produce characteristic effects on membrane potentials, currents, and cell contractions that were unrelated to significant changes in ICa. L-PC reduces surface negative charge of erythrocytes and myocytes (C. Gruver and A. J. Pappano, J. Mol. Cell. Cardiol. 25: 1275–1284, 1993), and we speculate that L-PC inhibits INa/K by this mechanism.


1989 ◽  
Vol 94 (3) ◽  
pp. 511-537 ◽  
Author(s):  
D C Gadsby ◽  
M Nakao

Whole-cell currents were recorded in guinea pig ventricular myocytes at approximately 36 degrees C before, during, and after exposure to maximally effective concentrations of strophanthidin, a cardiotonic steroid and specific inhibitor of the Na/K pump. Wide-tipped pipettes, in combination with a device for exchanging the solution inside the pipette, afforded reasonable control of the ionic composition of the intracellular solution and of the membrane potential. Internal and external solutions were designed to minimize channel currents and Na/Ca exchange current while sustaining vigorous forward Na/K transport, monitored as strophanthidin-sensitive current. 100-ms voltage pulses from the -40 mV holding potential were used to determine steady-state levels of membrane current between -140 and +60 mV. Control experiments demonstrated that if the Na/K pump cycle were first arrested, e.g., by withdrawal of external K, or of both internal and external Na, then neither strophanthidin nor its vehicle, dimethylsulfoxide, had any discernible effect on steady-state membrane current. Further controls showed that, with the Na/K pump inhibited by strophanthidin, membrane current was insensitive to changes of external [K] between 5.4 and 0 mM and was little altered by changing the pipette [Na] from 0 to 50 mM. Strophanthidin-sensitive current therefore closely approximated Na/K pump current, and was virtually free of contamination by current components altered by the changes in extracellular [K] and intracellular [Na] expected to accompany pump inhibition. The steady-state Na/K pump current-voltage (I-V) relationship, with the pump strongly activated by 5.4 mM external K and 50 mM internal Na (and 10 mM ATP), was sigmoid in shape with a steep positive slope between about 0 and -100 mV, a less steep slope at more negative potentials, and an extremely shallow slope at positive potentials; no region of negative slope was found. That shape of I-V relationship can be generated by a two-state cycle with one pair of voltage-sensitive rate constants and one pair of voltage-insensitive rate constants: such a two-state scheme is a valid steady-state representation of a multi-state cycle that includes only a single voltage-sensitive step.


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