A voltage-dependent persistent sodium current in mammalian hippocampal neurons.

Abstract

Currents generated by depolarizing voltage pulses were recorded in neurons from the pyramidal cell layer of the CA1 region of rat or guinea pig hippocampus with single electrode voltage-clamp or tight-seal whole-cell voltageclamp techniques. In neurons in situ in slices, and in dissociated neurons, subtraction of currents generated by identical depolarizing voltage pulses before and after exposure to tetrodotoxin revealed a small, persistent current after the transient current. These currents could also be recorded directly in dissociated neurons in which other ionic currents were effectively suppressed. It was concluded that the persistent current was carded by sodium ions because it was blocked by TIX, decreased in amplitude when extraceUular sodium concentration was reduced, and was not blocked by cadmium. The amplitude of the persistent sodium current varied with clamp potential, being detectable at potentials as negative as -70 mV and reaching a maximum at ~-40 mV. The maximum amplitude at -40 mV in 21 cells in slices was -0.34 • 0.05 nA (mean • 1 SEM) and -0.21 • 0.05 nA in 10 dissociated neurons. Persistent sodium conductance increased sigmoidally with a potential between -70 and -30 mV and could be fitted with the Boltzmann equation, g = g~,/{1 + exp[(V' -V)/k)]}. The average g~, was 7.8 • 1.1 nS in the 21 neurons in slices and 4.4 • t.6 nS in the 10 dissociated cells that had lost their processes indicating that the channels responsible are probably most densely aggregated on or close to the soma. The half-maximum conductance occurred close to -50 mV, both in neurons in slices and in dissociated neurons, and the slope factor (k) was 5-9 mV. The persistent sodium current was much more resistant to inactivation by depolarization than the transient current and could be recorded at >50% of its normal amplitude when the transient current was completely inactivated.

Differential modulation of TTX-sensitive and TTX-resistant Na+ channels in spinal cord astrocytes following activation of protein kinase C

“…While those roles of glial Na+ channels are only speculative, the expression of TTX-R Na+ channels has been demonstrated in excitable cells (Rogart et al, 1989;Cribbs et al, 1990;Kallen et al, 1990;Yang et al, 1991;Sculptoreanu et al, 1992), including central (Ikeda and Schofield, 1987) and peripheral neurons (Kostyuk et al, 1981;Caffrey et al, 1992;Roy and Narahashi, 1992) and TTX-R Na+ currents have been implicated in the modulation of neuronal signals (French et al, 1990). If neuronal TTX-R currents are modulated in a similar fashion as described here for TTX-R Na+ currents in astrocytes, alterations in their activity would have profound effects on their signaling behavior.…”

Voltage-Dependent Enhancement of Electrical Coupling by a Subthreshold Sodium Current

“…One of these, and perhaps physiologically the most relevant, is responsible for ϳ80% of the total amplification and reflects the gradual activation of a subthreshold membrane conductance with the characteristics of a persistent Na ϩ current (Crill, 1996). That is, the voltage sensitivity (0.42 mV -1 ), membrane potential activation range (10 -15 mV above resting potential), susceptibility to TTX and QX-314, and prolonged time course in the presence of K ϩ channel blockers are typical of persistent Na ϩ currents described in fish (Watanabe et al, 2000;Berman et al, 2001;Doiron et al, 2003) and mammalian neurons (Hotson et al, 1979;Llinás and Sugimori, 1980;Staftsrom et al, 1982;French and Gage, 1985;Mac Vicar, 1985;Staftsrom et al, 1985;French et al, 1990;for review, see Crill, 1996). Although persistent Na ϩ currents represent a small (ϳ1%) noninactivating fraction of the total Na ϩ current, they have a significant functional impact because they are activated ϳ10 mV negative to the transient Na ϩ current, where few voltage-gated channels are activated and neuron input resistance is high (Crill, 1996).…”

Extracellular Calcium Modulates Persistent Sodium Current-Dependent Burst-Firing in Hippocampal Pyramidal Neurons

“…This agent blocks both transient Na ϩ current and I NaP in CA1 PCs (French et al, 1990). As illustrated in Figure 4 A, adding 0.1 M TTX to the saline caused a progressive block of the burst responses concurrent with an increase in spike threshold.…”

“…These subthreshold ADPs are readily blocked by TTX, but not by Ca 2ϩ channel blockers , suggesting that they are generated by I NaP , the activation threshold of which is slightly more negative than spike threshold (French et al, 1990). We tested the effects of lowering [Ca 2ϩ ] o on these potentials.…”