R. Noriega-Navarro a , O. Lopez-Charcas b , B. Hernández-Enríquez c , P.E. Reyes-Gutiérrez d ,

TASK channels belong to the family of K þ channels with 4 transmembrane segments and 2 pore domains (4TM/2P) per subunit. These channels have been related to apoptosis in cerebellar granule neurons (CGN), as well as cancer in other tissues. TASK current is regulated by hormones, neurotransmitters, anesthetics and divalent cations, which are not selective. Recently, there has been found some organic compounds that inhibit TASK current selectively. In order to find other modulators, we report here a group of five dihydropyrrolo(2,1-a)isoquinolines (DPIs), four of them with putative anticancer activity, that were evaluated on TASK-1 and TASK-3 channels. The compounds 1, 2 and 3 showed IC50 39% of the TASK-carried leak current. Finally, only compound 1 showed significant protection (w36%) against apoptotic death of CGN induced by K þ deprivation. These results suggest that DPI compounds could be potential candidates for designing new selective inhibitors of TASK channels.