Figure 1.

Self-sustained plateau depolarization, burst firing, and conditional bistable behaviors in Nav1.9+/+ DRG neurons (A) Representative current-clamp responses of a Nav1.9+/+ DRG neuron (25 pF) to 100 ms current pulse injection. Steady bias current (−85 pA) was injected to hyperpolarize the cell to between −87 and −92 mV. Injected current pulse was varied in amplitude with 10 pA increments. Note that low intensity pulses elicited passive RC-circuit type responses whereas above-threshold depolarizing pulses triggered self-sustained plateau depolarization and repetitive firing. The asterisk indicates threshold potential for the slow regenerative response and the arrow shows the termination of the plateau phase, which is often followed by a postexcitatory hyperpolarization. (Inset) The same cell was subjected to slow voltage ramp from −100 to +10 mV. Note the “W-shaped” I-V relationship. (B) Spontaneous transitions between quiescent and firing states in a Nav1.9+/+ DRG neuron (27 pF). Application of bias current (−72 pA) revealed spontaneous bursting behavior, characterized by regenerative plateau depolarization carrying trains of action potentials and separated by silent states. (C) The time scale of the third burst in B is enlarged to illustrate the plateau depolarization and its relationship with the corresponding I-V curve. (D) Electrical activity recorded from a Nav1.9+/+ DRG neuron (33 pF) in response to a 300-ms hyperpolarizing current injection (−55 pA) applied with a −50-pA bias current. Four successive sweeps, each lasting 5,318 ms, have been superimposed to show the transition between bursting activity and silent state. The neuron showed either prolonged periods of membrane depolarization carrying trains of action potentials or remained silent at ∼−85 mV. Transition between the two states was induced by applying pulse hyperpolarizations, which either deactivated the plateau-generating system or promoted rebound excitation. (E) Families of superimposed membrane potential changes evoked by a series of current pulse injection in a Nav1.9+/+ DRG neuron (27 pF). Membrane potential was adjusted manually to between −35 and −40 mV by DC bias, immediately after conditioning Vm at −90 mV. Note that step increase in injected hyperpolarizing current caused linear response, up to a critical value at which a large active hyperpolarization occurred. Rebound depolarization followed a sigmoid-like trajectory, indicative of a metastable state. Recordings made using the intracellular solution 2 (Table I; 0 mM CsCl, 30 mM CsF, 100 mM KCl).

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