Figure 8.

iFGF14 shifts the voltage dependence of steady-state inactivation of the Nav currents in cerebellar Purkinje neurons. Whole-cell voltage-clamp recordings were obtained at 33 ± 1°C from WT and Fgf14^−/− Purkinje neurons in acute cerebellar slices as described in Materials and Methods. A, Representative recordings of Nav currents (left) evoked in a WT cerebellar Purkinje neuron from various conditioning voltages; the voltage-clamp paradigm is illustrated above the records and the currents are shown in the color of the corresponding voltage step. Note that the persistent currents were digitally subtracted (see Materials and Methods) and only the inactivating, transient components of the currents are shown. The transient Nav currents evoked at 0 mV were measured and normalized (in the same cell) to the current evoked from the most hyperpolarized test potential (of −110 mV). Mean ± SEM normalized transient Nav current amplitudes in WT and Fgf14^−/− Purkinje neurons were then plotted (right) as a function of the conditioning membrane potential and fitted using a Boltzmann equation (see Materials and Methods). The transient Nav current is inactivated at a significantly (p < 0.001) more hyperpolarized membrane potential in Fgf14^−/− (V_1/2 = −71.1 ± 0.9 mV, slope = 11.3 ± 1.0; n = 10), than in WT (V_1/2 = −58.1 ± 0.9 mV, slope = 10.3 ± 1.0; n = 11) Purkinje neurons. B, Representative recordings of the transient and persistent Nav currents (left) evoked in a WT Purkinje neuron at various test potentials; the voltage-clamp paradigm is illustrated above the records and the currents are shown in the color of the corresponding voltage step; the raw, unsubtracted current records used to quantify the transient and persistent compoents of the Nav currents are shown in the inset. The transient and persistent Nav conductances for the currents evoked at each test potential were determined and normalized (in the same cell) to the maximal transient and persistent Nav conductances and mean ± SEM normalized transient and persistent Nav conductances in WT and Fgf14^−/− Purkinje neurons were plotted (right) as a function of the test potential. Although well described by single Boltzmann functions (see Materials and Methods), the voltage dependences of activation of both the transient and the persistent components of the Nav currents (right) are similar in WT and Fgf14^−/− Purkinje neurons.