Modulation of the conductance-voltage relationship of the BK(Ca) channel by shortening the cytosolic loop connecting two RCK domains.
Calcium-dependent gating of large-conductance calcium-activated potassium (BK(Ca)) channels is mediated by the intracellular carboxyl terminus, which contains two domains of regulator of K(+) conductance (RCK). In mammalian BK(Ca) 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 BK(Ca) channel can be modulated by altering the tension of this loop region.
Lee
Ju-Ho
JH
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea.
Kim
Hyun-Ju
HJ
Kim
Hae-Deun
HD
Lee
Byoung-Cheol
BC
Chun
Jang-Soo
JS
Park
Chul-Seung
CS
D000595:Amino Acid Sequence; D000818:Animals; D019921:Biotinylation; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003720:Densitometry; D015151:Immunoblotting; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017385:Sequence Homology
C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels