Key result
Charge neutralization in one voltage-sensing segment (S2 or S4) of the human BKCa channel reciprocally impaired the voltage dependence of its neighboring segment, demonstrating functional cooperativity.
This biophysical study demonstrates that the S2 and S4 segments of the human BKCa voltage sensor domain functionally interact, proposing mechanical coupling and dynamic field focusing as mechanisms for this cooperativity.
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No immediate clinical implications for ion channel therapies; leaves open cooperativity in native mammalian cardiovascular models.
Pantazis et al. (2010) studied BKCa channel voltage sensor operation. Charge-neutralizing mutations (D153Q in S2, R213G in S4) vs. Channels with intact voltage sensors was evaluated on Voltage dependence of conformational changes (effective charge and half-activation potential). Charge neutralization in one voltage-sensing segment (S2 or S4) of the human BKCa channel reciprocally impaired the voltage dependence of its neighboring segment, demonstrating functional cooperativity.
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