1. ¹Institute of Biomechanics and Medical Engineering, Tsinghua University, Beijing 100084, PR China;
2. ²Department of Physiology, Nagoya University Graduate School of Medicine School, 65 Tsurumai, Nagoya 466-8550, Japan;
3. ³International Cooperative Research Project / Solution Oriented Research for Science and Technology, Cell Mechanosensing Project, Japan Science and Technology Agency, Nagoya 466-8550, Japan;
4. ⁴Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan

Correspondence: Hucheng Zhao, E-mail: zhaohc@mail.tsinghua.edu.cn; Masahiro Sokabe, E-mail: msokabe@med.nagoya-u.ac.jp

Received 14 October 2007; Revised 3 January 2008; Accepted 18 February 2008.

Abstract

Some large-conductance Ca²⁺ and voltage-activated K⁺(BK) channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca²⁺ to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive (MS) BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel (SAKCaC), and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca²⁺. However, the voltage and Ca²⁺ sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca²⁺ concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.