Novel description of ionic currents recorded with the action potential clamp technique: application to excitatory...

The traditional method of recording ionic currents in neurons has been with voltage-clamp steps. Other waveforms such as action potentials (APs) can be used. The AP clamp method reveals contributions of ionic currents that underlie excitability during an AP (Bean BP. Nat Rev Neurosci 8: 451-465, 2007). A novel usage of the method is described in this report. An experimental recording of an AP from the literature is digitized and applied computationally to models of ionic currents. These results are compared with experimental AP-clamp recordings for model verification or, if need be, alterations to the model. The method is applied to the tetrodotoxin-sensitive sodium ion current, INa, and the calcium ion current, ICa, from suprachiasmatic nucleus (SCN) neurons (Jackson AC, Yao GL, Bean BP. J Neurosci 24: 7985-7998, 2004). The latter group reported voltage-step and AP-clamp results for both components. A model of INa is constructed from their voltage-step results. The AP clamp computational methodology applied to that model compares favorably with experiment, other than a modest discrepancy close to the peak of the AP that has not yet been resolved. A model of ICa was constructed from both voltage-step and AP-clamp results of this component. The model employs the Goldman-Hodgkin-Katz equation for the current-voltage relation rather than the traditional linear dependence of this aspect of the model on the Ca(2+) driving force. The long-term goal of this work is a mathematical model of the SCN AP. The method is general. It can be applied to any excitable cell.