Regulation by second messengers of the slowly activating, voltage‐dependent potassium current expressed in Xenopus oocytes.

1. Voltage‐clamp recordings of membrane current were made from Xenopus oocytes that had been injected with RNA which had been transcribed in vitro from a cloned complementary DNA. 2. Depolarization from ‐80 mV evoked outward potassium currents that developed very slowly. At ‐20 mV the time constant for activation was about 50 s, and at +40 mV about 6 s. 3. The potassium current was increased by the calcium ionophore A23187 or by intracellular injection of inositol 1,4,5‐trisphosphate (IP3), each of which should increase the intracellular calcium concentration ([Ca2+]i). The current was decreased by injection of BAPTA (1,2‐bis(2‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid). The current was also reduced by phorbol esters; this effect was blocked by staurosporine. 4. In oocytes that had also been injected with RNA encoding the 5‐hydroxytryptamine (5‐HT2) receptor, 5‐HT increased the potassium current. After caffeine pretreatment, to block the release of intracellular calcium, 5‐HT decreased the current; this decrease was prevented by staurosporine. 5. It is concluded that the slowly activating, voltage‐dependent potassium current expressed in Xenopus oocytes is increased by increases in [Ca2+]i and is decreased by activation of protein kinase C. Stimulation of 5‐HT2 receptors can have both these effects, but the former normally predominates.