In Xenopus oocytes, Ca2+ influx through an endogenous voltage-gated Ca2+ channel activates a transient outward Cl− current (I CI(Ca)), which is potentiated by cAMP increase. The site of cAMP effect appears to be the Ca2+ channel instead of the Ca2+-activated Cl− channel, because cAMP potentiates the Ba2+ current through the Ca2+ channel in a similar way to the I Cl(Ca), and cAMP does not potentiate the Ca2+-dependent CI− current in cells treated with Ca2+ ionophore. Using the catalytic subunit of protein kinase A (PKA) and PKA inhibitors, it was shown that PKA is both necessary and sufficient for the cAMP effect on I CI(Ca). Furthermore, the cAMP/PKA-mediated potentiation of I cI(Ca) was inhibited by both type 1 and type 2A protein phosphatases.