Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
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Intracellular cAMP-modulated Gate in Hyperpolarization Activated Cation Channels

  • Park, Kyung-Joon (Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyunghee University) ;
  • Shin, Ki-Soon (Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyunghee University)
  • Published : 2007.12.31
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Abstract

Hyperpolarization-activated nonselective cation channels (HCNs) play a pivotal role in producing rhythmic electrical activity in the heart and the nerve cells. In our previous experiments, voltage-dependent $Cd^{2+}$ access to one of the substituted cysteines in S6, T464C, supports the existence of an intracellular voltage-dependent activation gate. Direct binding of intracellular cAMP to HCN channels also modulates gating. Here we attempted to locate the cAMP-modulated structure that can modify the gating of HCN channels. SpHCN channels, a sea urchin homologue of the HCN family, became inactivated rapidly and intracellular cAMP removed this inactivation, resulting in about eight-fold increase of steady-state current level. T464C was probed with $Cd^{2+}$ applied to the intracellular side of the channel. We found that access of $Cd^{2+}$ to T464C was strongly gated by cAMP as well as voltage. Release of bound $Cd^{2+}$ by DMPS was also gated in a cAMP-dependent manner. Our results suggest the existence of an intracellular cAMP-modulated gate in the lower S6 region of spHCN channels.

Keywords

References

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