摘要：

The effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), an activator of soluble guanylyl cyclase, on ionic currents have been assessed in rat pituitary GH3 lactotrophs. In GH3 cells bathed in normal Tyrode's solution, YC-1 (1 μM) reversibly suppressed the amplitude of the Ca2+-activated K+ current (IK(Ca)). YC-1 at a concentration above 10 μM produced a biphasic response in the amplitude of IK(Ca), i.e., an initial decrease followed by a sustained increase. When the pipette solutions were filled with high EGTA (10 mM), the YC-1-induced stimulatory effect on IK(Ca) was abolished. Over a similar concentration range, YC-1 also effectively inhibited the voltage-dependent K+ current (IK(V)) in GH3 cells. The IC50 value required for the inhibition of IK(V) by YC-1 was 1 μM. Unlike YC-1, 8-bromo cGMP did not inhibit IK(Ca). However, YC-1 (10 μM) did not affect the amplitude of L-type Ca2+ current. In the cell-attached configuration, application of YC-1 (10 μM) to the bath did not change the single-channel conductance of the large-conductance Ca2+-activated K+ (BKCa) channels; however, it did increase the opening probability of BKCa channels. In contrast, in the outside-out configuration, YC-1 (10 μM) significantly suppressed the opening probability of BKCa channels. The present study shows dual effects of YC-1 on IK(Ca) in GH3 cells. The YC-1-mediated stimulation of IK(Ca) may result from elevated cytosolic Ca2+, whereas the inhibition of IK(Ca) and IK(V) by YC-1 appears to be direct and independent of the activation of soluble guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated response to the activation of soluble guanylyl cyclase.

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