학술논문
A family of hyperpolarization-activated channels selective for protons
Document Type
Report
Author
Source
Proceedings of the National Academy of Sciences of the United States. June 16, 2020, Vol. 117 Issue 24, p13783, 9 p.
Subject
Language
English
ISSN
0027-8424
Abstract
Proton ([H.sup.+]) channels are special: They select protons against other ions that are up to a millionfold more abundant. Only a few proton channels have been identified so far. Here, we identify a family of voltage-gated 'pacemaker' channels, HCNL1, that are exquisitely selective for protons. HCNL1 activates during hyperpolarization and conducts protons into the cytosol. Surprisingly, protons permeate through the channel's voltage-sensing domain, whereas the pore domain is nonfunctional. Key to proton permeation is a methionine residue that interrupts the series of regularly spaced arginine residues in the S4 voltage sensor. HCNL1 forms a tetramer and thus contains four proton pores. Unlike classic HCN channels, HCNL1 is not gated by cyclic nucleotides. The channel is present in zebrafish sperm and carries a proton inward current that acidifies the cytosol. Our results suggest that protons rather than cyclic nucleotides serve as cellular messengers in zebrafish sperm. Through small modifications in two key functional domains, HCNL1 evolutionary adapted to a low-[Na.sup.+] freshwater environment to conserve sperm's ability to depolarize. HCNL1 channel | proton channel | voltage-sensing domain | HCN channel