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Effects of ${\alpha}_1-Adrenergic$ Receptor Stimulation on Intracellular $Na^+$ Activity and Twitch Force in Guinea-Pig Ventricular Muscles

Chae, Soo-Wan   (Department of Pharmacology, Chonbuk National UniversityUU0001120  ); Gong, Q.Y.    (Department of Pharmacology, Shanghai Medical University   ); Wang, D.Y.    (Department of Life Science, Pohang University of Science and Technology   ); Lee, Chin-O.   (Department of Life Science, Pohang University of Science and TechnologyUU0001353  );
  • 초록

    The effects of ${\alpha}_1-adrenergic$ receptor stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force were investigated in ventricular muscles from guinea-pig hearts. Action potentials, intracellular $Na^+$ activity, and twitch force of ventricular papillary muscles were measured simultaneously under various experimental conditions. Stimulation of the ${\alpha}_1-adrenergic$ receptor by phenylephrine produced variable changes in action potential duration, a slight hyperpolarization of the diastolic membrane potential, a decrease in intracellular $Na^+$ activity, and a biphasic inotropic response in which a transient negative inotropic response was followed by a sustained positive inotropic response. These changes were blocked by prazosin, an antagonist of the ${\alpha}_1-adrenergic$ receptor, but not by atenolol, an antagonist of the ${\beta}-adrenergic$ receptor. This indicates that the changes in membrane potential, intracellular $Na^+$ activity, and twitch force are mediated by stimulation of the ${\alpha}_1-adrenergic$ receptor, but not by stimulation of ${\beta}-adrenergic$ receptor. The decrease in intracellular $Na^+$ activity was not observed in quiescent muscles, depending on the rate of the action pontentials in beating muscles. The intracellular $Na^+$ activity decrease was substantially inhibited by tetrodotoxin. However, the decrease in intracellular $Na^+$ activity was not affected by an inhibition of the $Na^+-K^+$ pump. Therefore, the decrease in intracellular $Na^+$ activity mediated by the ${\alpha}_1-adrenergic$ receptor appears to be due to a reduction of $Na^+$ influx during the action potential, perhaps through tetrodotoxin sensitive $Na^+$ channels. Our study also revealed that the decrease in intracellular $Na^+$ activity might be related to the transient negative inotropic response. The intracellular $Na^+$ activity decrease could lower intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchanger and thereby produce a decline in twitch force.


  • 주제어

    Guinea-pig ventricle .   ${\alpha}_1-adrenergic$ receptor, Intracellular $Na^+$ activity .   Membrane potential .   Twitch force .   Biphasic inotropic response .   Phenylephrine .   Prazosin.  

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