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 hip-pocampus with single electrode voltage-clamp or tight-seal whole-cell voltage-clamp techniques. In neurons in situ in slices, and in dissociated neurons, subtrac-tion 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 var-ied 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

Iron-Responsive Olfactory Uptake of Manganese Improves Motor Function Deficits Associated with Iron Deficiency

Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor D1 (D1R) levels were reduced and dopamine receptor D2 (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed “rescue response” with beneficial influence on motor impairment due to low iron status