Endothelin augments unitary calcium channel currents on the smooth muscle cell membrane of guinea‐pig portal vein.

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Abstract
1. The effects of endothelin (ET) on the Ca2+ channel current in smooth muscle cells of the guinea‐pig portal vein were investigated using the patch‐clamp technique with whole‐cell and cell‐attached configurations. 2. ET augmented the macroscopic Ba2+ current in a dose‐dependent manner; this effect was inhibited by nifedipine or Cd2+. Augmentation of the inward current by ET did not depend on the amplitude of the depolarizing pulse. Further, when the membrane potential was held at ‐60 mV, ET increased the amplitude of the Ba2+ inward current measured at the peak and end of the depolarizing pulse to the same extent. 3. By contrast, when the membrane potential was held at ‐80 mV, depolarizing pulses to potentials more negative than 0 mV produced greater augmentation of the inward current than did those more positive than 0 mV. Moreover, when a depolarizing pulse to below 0 mV was applied, ET increased the peak amplitude of the inward current more than the amplitude measured at the end of pulse. 4. Using the patch‐clamp technique with cell‐attached configuration, two types of unitary Ba2+ current with conductances of 22 and 12 pS were obtained in 50 mM‐Ba2+ solution. Nifedipine inhibited both types of unitary channel current, but the sensitivity of the 22 pS Ca2+ channel to nifedipine was 20‐fold higher than the 12 pS Ca2+ channel. 5. Bath application of ET prolonged the mean open time, reduced the number of sweeps in which no Ca2+ channel was opened ('blank' sweep), and increased the number of channel openings evoked by each depolarizing pulse without changes of conductance. As a consequence, ET increased the open probability of both channels. 6. Augmentation of the 12 pS channels by ET was seen only in the early phase of a depolarizing pulse (57 ms from the onset of 170 ms pulse), while augmentation of the 22 pS channels was seen during the entire period of a depolarizing pulse. 7. When ET was added to the pipette solution, the activity of both Ca2+ channels was increased. However, this effect was less frequently observed than when ET was applied in the bath. 8. These results suggest that ET augments both the nifedipine‐sensitive and resistant Ca2+ channels in the smooth muscle cell membrane of the guinea‐pig portal vein, but in different ways. Presumably, ET acts indirectly on the voltage‐dependent Ca2+ channel.