RT Journal Article
SR Electronic
T1 Calcium-driven regulation of voltage-sensing domains in BK channels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 520429
DO 10.1101/520429
A1 Yenisleidy Lorenzo-Ceballos
A1 Willy Carrasquel-Ursulaez
A1 Karen Castillo
A1 Osvaldo Alvarez
A1 Ramon Latorre
YR 2019
UL http://biorxiv.org/content/early/2019/01/16/520429.abstract
AB Allosteric interplays between voltage-sensing domains (VSD), Ca2+-binding sites, and the pore domain govern the Ca2+- and voltage-activated K+ (BK) channel opening. However, the functional relevance of the Ca2+- and voltage-sensing mechanisms crosstalk on BK channel gating is still debated. We examined the energetic interaction between Ca2+ binding and VSD activation measuring and analyzing the effects of internal Ca2+ on BK channels gating currents. Our results indicate that the Ca2+ sensors occupancy has a strong impact on the VSD activation through a coordinated interaction mechanism in which Ca2+ binding to a single α-subunit affects all VSDs equally. Moreover, the two distinct high-affinity Ca2+-binding sites contained in the C-terminus domains, RCK1 and RCK2, appear to contribute equally to decrease the free energy necessary to activate the VSD. We conclude that voltage-dependent gating and pore opening in BK channels is modulated to a great extent by the interaction between Ca2+ sensors and VSDs.