Using isolated myocytes from the rat tail artery, whole cell voltage clamp studies were undertaken to assess the contribution of a non-selective cation conductance (NSCC) to contraction in response to the aradrenoceptor agonist phenylephrine. Holding the cell at a voltage beyond the range for a sustained influx of Ca2+ via the L-type voltage-gated Ca2+ ion channel (VGCC), we determined that low concentrations of phenylephrine activate an inward current which is not blocked by the VGCC blocker nifedipine, but is reduced when extracellular Na+ (60 mM) is replaced with choline. Using digital subtraction of data obtained in the presence and absence of phenylephrine, we determined that this inward current reversed around 0 mV as would be expected of a non-selective cation conductance. The shift in zero current potential elicited by phenylephrine was identical to the degree of depolarization observed using microelectrode recordings in de-endothelialized rat tail artery strips. By holding the cells at E(K) and replacing extracellular Cl-(60 mM) with gluconate, the presence of this inward current was confirmed, eliminating a role for K+ or Cl- as major charge carriers. These data suggest that phenylephrine activates a NSCC to elicit depolarization of the vascular tissue, which may subsequently depolarize the membrane potential to within the voltage range for a sustained entry of Ca2+ via the VGCC, thereby accounting for the nifedipine sensitivity of the whole tissue.
|Number of pages||2|
|Journal||Proceedings of the Western Pharmacology Society|
|Publication status||Published - 1 Dec 1998|
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