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Correspondence to Ramon Latorre: rlatorre{at}cecs.cl
High conductance, calcium- and voltage-activated potassium (BK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (ß) subunits. ß1 and ß2 subunits increase apparent channel calcium sensitivity. The ß1 subunit also decreases the voltage sensitivity of the channel and the ß2 subunit produces an N-type inactivation of BK currents. We further characterized the effects of the ß1 and ß2 subunits on the calcium and voltage sensitivity of the channel, analyzing the data in the context of an allosteric model for BK channel activation by calcium and voltage (Horrigan and Aldrich, 2002). In this study, we used a ß2 subunit without its N-type inactivation domain (ß2IR). The results indicate that the ß2IR subunit, like the ß1 subunit, has a small effect on the calcium binding affinity of the channel. Unlike the ß1 subunit, the ß2IR subunit also has no effect on the voltage sensitivity of the channel. The limiting voltage dependence for steady-state channel activation, unrelated to voltage sensor movements, is unaffected by any of the studied ß subunits. The same is observed for the limiting voltage dependence of the deactivation time constant. Thus, the ß1 subunit must affect the voltage sensitivity by altering the function of the voltage sensors of the channel. Both ß subunits reduce the intrinsic equilibrium constant for channel opening (L0). In the allosteric activation model, the reduction of the voltage dependence for the activation of the voltage sensors accounts for most of the macroscopic steady-state effects of the ß1 subunit, including the increase of the apparent calcium sensitivity of the BK channel. All allosteric coupling factors need to be increased in order to explain the observed effects when the 
subunit is coexpressed with the ß2IR subunit.
Key Words: BK channel • ß subunits • allosteric model • voltage dependence • apparent calcium sensitivity
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