Abstract
Large conductance Ca2+-activated K+ (BK) channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv) channels characterized by having six (S1-S6) transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0) transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 microM-100 microM) in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.
Highlights
Large conductance Ca2+-activated K+ (BK) channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv) channels characterized by having six (S1-S6) transmembrane domains and a positively charged S4 domain
Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+
When Mario Luxoro asked me (RL) to write a chapter in this issue of Biological Research dedicated to my teacher, colleague, and friend, Eduardo Rojas, I immediately thought that the best present for him would be to say something about the ion channel that is closest to my heart
Summary
If you ask me (RL) why the laboratory in Montemar was so important in the development of biophysics in Chile, I would immediately say: because the seniors were doing good science, and they let the juniors to do whatever they wanted In this regard, our professors made it clear from the onset of our research work that we were supposed to take one idea from the many floating around in the lab in those years and develop the experimental and theoretical framework in an absolutely independent manner. Discussions about science, lab space, or politics were frequently heated and always won by Fernando Vargas because during the course of a debate he never lost his temper, and his logic was unbeatable There was another lesson for us: scientists are generally passionate people who defend their territories and pet ideas as ferociously as bears. His generosity and kindness made possible for me to be telling you my part of the Montemar adventure
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