Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters.
Connexin mimetic peptides are widely used to assess the contribution of nonjunctional connexin channels in several processes, including ATP release. These peptides are derived from various connexin sequences and have been shown to attenuate processes downstream of the putative channel activity. Yet so far, no documentation of effects of peptides on connexin channels has been presented. We tested several connexin and pannexin mimetic peptides and observed attenuation of channel currents that is not compatible with sequence specific actions of the peptides. Connexin mimetic peptides inhibited pannexin channel currents but not the currents of the channel formed by connexins from which the sequence was derived. Pannexin mimetic peptides did inhibit pannexin channel currents but also the channels formed by connexin 46. The same pattern of effects was observed for dye transfer, except that the inhibition levels were more pronounced than for the currents. The channel inhibition by peptides shares commonalities with channel effects of polyethylene glycol (PEG), suggesting a steric block as a mechanism. PEG accessibility is in the size range expected for the pore of innexin gap junction channels, consistent with a functional relatedness of innexin and pannexin channels.
Wang
Junjie
J
Dept. of Physiology and Biophysics, Univ. of Miami, School of Medicine, PO Box 016430, Miami FL 33101, USA.
Ma
Meiyun
M
Locovei
Silviu
S
Keane
Robert W
RW
Dahl
Gerhard
G
D000818:Animals; D002118:Calcium / Q000502:physiology; D018031:Connexin 43 / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017630:Connexins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D017629:Gap Junctions / Q000737:chemistry* / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis; D000097002:Gap Junction beta-1 Protein
D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D009419:Nerve Tissue Proteins; D010455:Peptides; D000097002:Gap Junction beta-1 Protein; C492764:PANX1 protein, human; C082917:GJA3 protein, human