Thermodynamics of activation gating in olfactory-type cyclic nucleotide-gated (CNGA2) channels.
Olfactory-type cyclic nucleotide-gated (CNG) ion channels open by the binding of cyclic nucleotides to a binding domain in the C-terminus. Employing the Eyring rate theory, we performed a thermodynamic analysis of the activation gating in homotetrameric CNGA2 channels. Lowering the temperature shifted the concentration-response relationship to lower concentrations, resulting in a decrease of both the enthalpy DeltaH and entropy DeltaS upon channel opening, suggesting that the order of an open CNGA2 channel plus its environment is higher than that of the closed channel. Activation time courses induced by cGMP concentration jumps were used to study thermodynamics of the transition state. The activation enthalpies DeltaH++ were positive at all cGMP concentrations. In contrast, the activation entropy DeltaS++ was positive at low cGMP concentrations and became then negative at increasing cGMP concentrations. The enthalpic and entropic parts of the activation energies approximately balance each other at all cGMP concentrations, leaving the free enthalpy of activation in the range between 19 and 21 kcal/mol. We conclude that channel activation proceeds through different pathways at different cGMP concentrations. Compared to the unliganded channel, low cGMP concentrations generate a transitional state of lower order whereas high cGMP concentrations generate a transitional state of higher order.
Institut für Physiologie II, Friedrich-Schiller-Universität Jena, Jena, Germany.
Vasilica
V
Nache
Jana
J
Kusch
Christoph
C
Biskup
Eckhard
E
Schulz
Thomas
T
Zimmer
Volker
V
Hagen
Klaus
K
Benndorf
D000818:Animals; D001665:Binding Sites; D006152:Cyclic GMP / Q000494:pharmacology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019277:Entropy; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008024:Ligands; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D014982:Xenopus laevis / Q000378:metabolism
D054815:Cyclic Nucleotide-Gated Cation Channels; D008024:Ligands; D006152:Cyclic GMP