Quantification of exponential Na+ current activation in N-bromoacetamide-treated cardiac myocytes of guinea-pig.

1. Time courses for the uptake of L-lactate, D-lactate and pyruvate into isolated cardiac ventricular myocytes from guinea pig were determined at 11 degrees C or 0 degrees C (for pyruvate) in a citrate-based buffer by using a silicone-oil-filtration technique. These conditions enabled initial rates of transport to be measured without interference from metabolism of the substrates. 2. At a concentration of 0.5 mM, transport of all these substrates was inhibited by approx. 90% by 5 mM-alpha-cyano-4-hydroxycinnamate; at 10 mM-L-lactate a considerable portion of transport could not be inhibited. 3. Initial rates of L-lactate and pyruvate uptake in the presence of 5 mM-alpha-cyano-4-hydroxycinnamate were linearly related to the concentration of the monocarboxylate and probably represented diffusion of the free acid. The inhibitor-sensitive component of uptake obeyed Michaelis-Menten kinetics, with Km values for L-lactate and pyruvate of 2.3 and 0.066 mM respectively. 4. Pyruvate and D-lactate inhibited the transport of L-lactate, with Ki values (competitive) of 0.077 and 6.6 mM respectively; the Ki for pyruvate was very similar to its Km for transport. The Ki for alpha-cyano-4-hydroxycinnamate as a non-competitive inhibitor was 0.042 mM. 5. These results indicate that L-lactate, D-lactate and pyruvate share a common carrier in guinea-pig cardiac myocytes; the low stereoselectivity for L-lactate over D-lactate and the high affinity for pyruvate distinguish it from the carrier in erythrocytes and hepatocytes. The metabolic roles for this novel carrier in heart are discussed.

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Effects of class III antiarrhythmic agents on muscarinic receptor-mediated action potential shortening and K+ current activation in guinea-pig atrial cells.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)50326-2 ◽

1994 ◽

Vol 64 ◽

pp. 171

Author(s):

Katsumi Mori ◽

Yukio Hara ◽

Haruaki Nakaya

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Muscarinic Receptor ◽

Antiarrhythmic Agents ◽

Class Iii ◽

Mediated Action ◽

Atrial Cells ◽

Current Activation ◽

K Current ◽

Action Potential Shortening

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Inhibition by a dilazep derivative, K-7259, of the Na+ current in guinea-pig ventricular myocytes

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)34561-5 ◽

1999 ◽

Vol 79 ◽

pp. 137

Author(s):

Min Chen ◽

Kazuto Yazawa ◽

Chun-Yang Xiao ◽

Hiroko Hashizume ◽

Fumitaka Ushikubi ◽

...

Keyword(s):

Guinea Pig ◽

Ventricular Myocytes ◽

Na Current

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Effects of sevoflurane on inward rectifier K+ current in guinea pig ventricular cardiomyocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.1.h324 ◽

1997 ◽

Vol 273 (1) ◽

pp. H324-H332 ◽

Cited By ~ 2

Author(s):

A. Stadnicka ◽

Z. J. Bosnjak ◽

J. P. Kampine ◽

W. M. Kwok

Keyword(s):

Steady State ◽

Guinea Pig ◽

Outward Current ◽

Inward Rectifier ◽

Equilibrium Potential ◽

Ventricular Cardiomyocytes ◽

Steady State Current ◽

Voltage Dependent ◽

Current Activation ◽

Extracellular Side

The effects of sevoflurane on the inward rectifier potassium current (IKIR) were examined in guinea pig ventricular cardiomyocytes using the whole cell patch-clamp methodology. Sevoflurane had a unique dual effect on the steady-state current amplitude, producing a reversible, concentration- and voltage-dependent block of the inward current at potentials negative to the potassium equilibrium potential (EK) but enhancing the outward current positive to EK. Accordingly, the steady-state conductance negative to EK was reduced by sevoflurane, but conductance positive to EK was increased. The chord conductance-voltage relationship showed depolarizing shifts at 0.7, 1.3, and 1.6 mM sevoflurane. When the myocytes were dialyzed with 10 mM Mg2+, but not with 1.0 mM Mg2+, sevoflurane further slowed current activation kinetics. With 10 mM intracellular Mg2+, the outward current enhancement by sevoflurane and the associated shifts in half-activation potential were abolished. Polyamines abolished all effects of sevoflurane on IKIR. With the use of the Woodhull model for voltage-dependent block, we determined the sevoflurane interaction site with the inward rectifier potassium channel to be at an electrical distance of 0.2 from the extracellular side.

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