Distinct effects of Ca2+ and voltage on the activation and deactivation of cloned Ca2+-activated K+ channels

1. Cloned large-conductance Ca2+-activated K+ channels from Drosophila (dslo) and human (hslo) were expressed in Xenopus oocytes. The effects of Ca2+ and voltage on these channels were compared by analysing both macroscopic currents and single-channel transitions. 2. The activation kinetics of dslo Ca2+-activated K+ channels are strongly influenced by the intracellular Ca2+ concentration, but are only minimally affected by membrane voltage. Current activation kinetics increase more than 60-fold in response to Ca2+ concentration increases in the range 0.56-405 mu M, but increase less than 2-fold by voltage changes from -60 to +80 mV. 3. The activation kinetics of hslo channels are similarly influenced by increases in Ca2+ concentration; however, these kinetics are also increased 5- to 10-fold by voltage changes from -60 to +80 mV. 4. The deactivation kinetics of both dslo and hslo channels are also more Ca2+ sensitive than voltage sensitive. Increasing concentrations of Ca2+ slow deactivation kinetics more than 40-fold, while changes in the membrane voltage cause less than 2-fold changes. 5. Ca2+ increases the activation kinetics by altering first latency distributions. Increasing the Ca2+ concentration from 0.56 to 2.4 mu M causes a 20-fold decrease in the mean time to first channel opening.