Ionic basis for action potential prolongation by phenylephrine in canine epicardial myocytes.
BACKGROUND
In canine ventricle, alpha-adrenergic agonists prolong action potential duration (APD) without any effect on the action potential notch, suggesting that, in this species, the effect on repolarization might be independent of inhibition of I(to). The present study investigated the action of the alpha-adrenergic agonist phenylephrine on the action potential and the repolarizing currents I(to) and I(K) in isolated canine epicardial myocytes.


RESULTS
Isolated cells from canine epicardial tissue, and Purkinje fibers, were studied with the whole cell, voltage clamp method. Phenylephrine 0.1 microM increased APD by 13% +/- 4% at 90% repolarization without affecting the notch or amplitude. Under voltage clamp, concentrations of phenylephrine as high as 10 microM had no effect on I(to) in canine epicardial myocytes. However, I(to) of isolated canine Purkinje myocytes was reduced to 69% +/- 7% of control by 1 microM phenylephrine. Further studies in canine epicardial myocytes revealed an action of phenylephrine to inhibit I(K), and in particular I(Ks). Using a voltage protocol that included a two-step repolarization to separate I(Ks) and I(Kr) tail components, the largely I(Kr) component was not significantly affected by 1 microM phenylephrine, whereas the largely I(Ks) component was reduced to 81% +/- 5% of control value.


CONCLUSIONS
Alpha-adrenergic prolongation of repolarization in canine epicardium does not result from inhibition of I(to). Rather, it appears that reduction of I(Ks) contributes to the action of phenylephrine. The unresponsiveness of epicardial I(to) is not a general characteristic of the canine heart, because Purkinje myocyte I(to) was inhibited, suggesting regional differences in the molecular basis of I(to) and/or alpha-adrenergic signaling in the canine heart.
Robinson
R B
RB
Department of Pharmacology, Columbia University, New York, New York 10032, USA. RBR1@columbia.edu
Liu
Q Y
QY
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D007477:Ions; D010496:Pericardium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D051668:Delayed Rectifier Potassium Channels; D007477:Ions; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D010656:Phenylephrine