Modulation of the Conductance-Voltage Relationship of the BKCa Channel by Shortening the Cytosolic Loop Connecting Two RCK Domains

作者：Lee Ju Ho; Kim Hyun Ju; Kim Hae Deun; Lee Byoung Cheol; Chun Jang Soo; Park Chul Seung^*

来源：Biophysical Journal, 2009, 97(3): 730-737.

DOI：10.1016/j.bpj.2009.04.058

Calcium-dependent gating of large-conductance calcium-activated potassium (BKCa) channels is mediated by the intracellular carboxyl terminus, which contains two domains of regulator of K conductance (RCK). In mammalian BKca channels, the two RCK domains are separated by a protein segment of 101 residues that is poorly conserved in evolution and predicted to have no regular secondary structures. We investigated the functional importance of this loop using a series of deletion mutations. We found that the length, rather than the specific sequence at the central region of the segment, is critical for the functionality of the channel. As the length of the loop is progressively shorted, the conductance-voltage relationship gradually shifts toward more positive voltages with a minimum length of 70 amino acids, in an apparent response to increased tension within the loop. Thus, the functional activity of the BKCa channel can be modulated by altering the tension of this loop region.

• 出版日期2009-8-5