Premium
The instantaneous component of HCN currents is selectively blocked by C. difficile Toxin B in rat L6‐S2 DRG
Author(s) -
Colomb Denis George,
Kang Minho,
Hamm Elaine E.,
Ballard Jimmy D.,
Tsiokas Leonidas,
Akbarali Hamid I.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a328
Subject(s) - hyperpolarization (physics) , chemistry , soma , hcn channel , gating , biophysics , membrane potential , neuroscience , stereochemistry , biochemistry , receptor , ion channel , biology , nuclear magnetic resonance spectroscopy
In non‐pacing cells, such as dorsal root ganglia (DRG) soma, hyperpolarization‐activated cyclic‐nucleotide gated non‐specific cation (HCN) channels are hypothesized to contribute to the resting membrane potential (RMP). HCN currents consist of an instantaneous (I Inst(HCN) ) and a slowly activating component (I HCN(Slow). In rat L6‐S2 DRG, I HCN(Slow) activated at potentials negative to −80 mV (p<0.05, n= 55) and was selectively (p<0.05) blocked by 3mM CsCl (n=45) or 10 u M ZD7288 (n=8). Inhibition of I HCN(Slow) did not result in a significant hyperpolarization of the RMP. To elucidate the role of I Inst(HCN) in defining the RMP we sought to identify a specific blocker of this component current. I Inst(HCN) was selectively inhibited in DRG soma following exposure to C.difficile Toxin B (5 u g/ u l; 10 min external perfusion) resulting in significant hyperpolarization of the RMP (p<0.05, n=5). Furthermore, in preliminary experiments Toxin‐B inhibited the instantaneous component of heterlogously expressed huHCN‐1 (HEK‐293). The ability to differentially block I Inst(HCN) and I HCN(Slow) suggests separate gating mechanisms for these component currents and defines the relevance of I Inst(HCN) in maintaining RMP.