A sequence in the carboxy-terminus of the α1C subunit important for targeting, conductance and open probability of L-type Ca2+ channels

The role of the 80-amino acid motif 1572-1651 in the C-terminal tail of alpha(1C) Ca2+ channel subunits was studied by comparing properties of the conventional alpha(1C,77) channel expressed in HEK-tsA201 cells to three isoforms carrying alterations in this motif, Replacement of amino acids 1572-1651 in alpha(1C,77) with 81 non-identical residues leading to alc,ss impaired membrane targeting and cluster formation of the channel. Similar to alpha(1C,86), substitution of its 1572-1598 (alpha(1C,77L)) or 1595-1652 (alpha(1C,77K)) segments into the alpha(1C,77) channel yielded single-channel Ba2+ currents with increased inactivation, reduced open probability and unitary conductance, when compared to the alc,77 channel. Thus, the C-terminal sequence 1572-1651 of the ale subunit is important for membrane targeting, permeation and open probability of L-type Ca2+ channels. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.