Gating molecule interactions in K+ channels. A consistent explanation for cole-moore shifts and potential ramp experiments

The enhanced induction period of potassium channel currents in squid giant axon induced by hyperpolarizing prepulses (the Cole-Moore shift) is observed and analyzed for a range of depolarizing step potentials. The induction periods produced when the axon is voltage clamped with ascending potential ramps are also analyzed since both sets of experiments are incompatible with fourth-power dependence proposed by Hodgkin and Huxley for the squid K⁺ channels. When the Hodgkin-Huxley equations are modified to include the effects of interactions between gating molecules within individual channels, both the Cole-Moore and ascending potential ramp data are described with a fourth-power dependence. The constant interaction parameters which provide a consistent fit for all the data are based on the geometrical arrangement of gating molecules within the channel and the total interaction energy which stabilizes the four gating molecules in their closed configuration. A tetrahedral gating molecule geometry and an interaction energy of only 471 cal/mole provide optimal fits of all the data; the modified equations retain the ability to describe data presently described by the Hodgkin-Huxley equations in the depolarizing regime.