A Novel Method for the Description of Voltage-Gated Ionic Currents Based on Action Potential Clamp Results—Application to Hippocampal Mossy Fiber Boutons

Action potential clamp (AP-clamp) recordings of the delayed rectifier K(+) current I K and the fast-activated Na(+) current I Na in rat hippocampal mossy fiber boutons (MFBs) are analyzed using a computational technique recently reported. The method is implemented using a digitized AP from an MFB and computationally applying that data set to published models of I K and I Na. These numerical results are compared with experimental AP-clamp recordings. The I Na result is consistent with experiment; the I K result is not. The difficulty with the I K model concerns the fully activated current-voltage relation, which is described here by the Goldman-Hodgkin-Katz dependence on the driving force (V-E K) rather than (V-E K) itself, the standard model for this aspect of ion permeation. That revision leads to the second-a much steeper voltage dependent activation curve for I K than the one obtained from normalization of a family of I K records by (V-E K). The revised model provides an improved description of the AP-clamp measurement of I K in MFBs compared with the standard approach. The method described here is general. It can be used to test models of ionic currents in any excitable cell. In this way it provides a novel approach to the relationship between ionic current and membrane excitability in neurons.