Mechanism of cGMP-gated channel block by intracellular polyamines.
Polyamines block the retinal cyclic nucleotide-gated channel from both the intracellular and extracellular sides. The voltage-dependent mechanism by which intracellular polyamines inhibit the channel current is complex: as membrane voltage is increased in the presence of polyamines, current inhibition is not monotonic, but exhibits a pronounced damped undulation. To understand the blocking mechanism of intracellular polyamines, we systematically studied the endogenous polyamines as well as a series of derivatives. The complex channel-blocking behavior of polyamines can be accounted for by a minimal model whereby a given polyamine species (e.g., spermine) causes multiple blocked channel states. Each blocked state represents a channel occupied by a polyamine molecule with characteristic affinity and probability of traversing the pore, and exhibits a characteristic dependence on membrane voltage and cGMP concentration.
Guo
D
D
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA.
Lu
Z
Z
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology*; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D011487:Protein Conformation; D011522:Protons; D011700:Putrescine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*; D014982:Xenopus laevis
D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D011522:Protons; D013096:Spermine; D006152:Cyclic GMP; D011700:Putrescine