Summary
Stimulation of α1-adrenoceptors evokes a different pattern of inotropic responses in atrial and ventricular heart muscle preparations from rats. The inotropic effects are accompanied by different changes in membrane potential. In an attempt to clarify the question whether or to which extent these events are causally related, the effects of phenylephrine on force of contraction, transmembrane potential, Ca2+ current (ICa) and K+ currents were comparatively studied in either tissue.
In atrial preparations, phenylephrine 10 μmol/l caused an increase in force of contraction, a marked prolongation of the action potential duration and a depolarization of the membrane at rest. In the ventricle, however, the addition of phenylephrine 10 μmol/l produced first a decline in force of contraction associated with a hyperpolarization of the membrane and a reduction in the action potential duration. These changes were followed by an increase in force,of contraction and a slight prolongation of the action potential, whereas the resting membrane potential remained increased. The hyperpolarization was eliminated in the presence of ouabain 100 μmol/l.
In enzymatically isolated atrial and ventricular myocytes, the whole-cell voltage clamp technique was used to study membrane currents on exposure to phenylephrine. Phenylephrine 30 μmol/l did not affect the magnitude of ICa in either cell type. Transient and steady state K+ outward currents, however, were significantly diminished to a similar extent in atrial and in ventricular myocytes.
It is concluded that the positive inotropic effect of α1-adrenoceptor stimulation in the rat atrium is related to an increase in action potential duration and a decrease in resting membrane potential due to a decrease in K+ currents. In the ventricle, phenylephrine additionally activates the Na+/K+ pump thereby hyperpolarizing the membrane. The rapid onset of pump stimulation seems to overwhelm, in the beginning, the phenylephrine-induced decrease in K+ conductance and therefore to evoke a transient negative inotropic effect.
It is assumed that phenylephrine can alter the intracellular Ca2+ concentration due to changes in the action potential duration. The way how Ca 2+ enters the cell remains speculative, since direct changes of Ica were not detected. The more complicated changes in membrane potential in the ventricle suggest that also other mechanisms for the positive inotropic response to phenylephrine must be considered.
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Ertl, R., Jahnel, U., Nawrath, H. et al. Differential electrophysiologic and inotropic effects of phenylephrine in atrial and ventricular heart muscle preparations from rats. Naunyn-Schmiedeberg's Arch Pharmacol 344, 574–581 (1991). https://doi.org/10.1007/BF00170655
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DOI: https://doi.org/10.1007/BF00170655