Propriétés biophysiques et pharmacologie des canaux KCa2

Small conductance calcium activated potassium channels (SK or KCa2) are implicated in the neuronal excitability by underlying after-hyperpolarisation of medium duration. We have used several techniques to explore the biophysics and the pharmacology of those channels.We have revealed the inhibition of the channels by extracellular protons, and we have identified interaction sites composed of histidine residues. A differential sensitivity to protons among two different sub-types was highlighted; it was due to the presence of an extra histidine on one sub-type sequence.In a second part, we have identified new interactions sites of apamin, which is the blocking agent of reference for KCa2 channels. We have also concluded that apamin is not a pore blocker, and proposed an allosteric block mechanism. In the last part, we have established that the 1,3-di-o-tolyl-guanidine (DTG), classically described as a σ agonist, was able to block the KCa2 channels. We have started to explore this molecule’s block mechanism, but the interaction site has not yet been identified.