With this model, inactivation is coupled in an allosteric manner

With this model, inactivation is coupled in an allosteric manner to activation but it is not obligatory

for channels to open for inactivation to occur (Armstrong, 2006). Parameters were adjusted by trial and error to match the voltage dependence and kinetics of activation and inactivation and voltage dependence of steady-state current, using the data from our experimental recordings of current from acutely dissociated hippocampal CA1 neurons at 37°C. Data are summarized as mean ± SEM. Thanks to Zayd Khaliq for discussion and helpful suggestions. Supported by the National Institute of Neurological Disorders and Stroke (R01-NS036855 to B.P.B., R01-NS046579 to B.L.S., F31-NS064630 to B.C.C., and F31-NS065647 to A.J.G.) and the Howard Hughes Medical Institute (B.L.S.). A.J.G. was also supported by a Quan Predoctoral Fellowship. “
“Astrocytes AZD9291 solubility dmso alone make and store glycogen in the mammalian adult brain (Cataldo and Broadwell, 1986). By recruiting this energy store, astrocytes can deliver lactate (and possibly pyruvate) to neurons for fuel, helping maintain axonal and synaptic function (Izumi et al., 1997; Magistretti

and Pellerin, 1999; Wender et al., 2000), particularly during brief periods of aglycemia (Wender et al., 2000) or during intense neuronal activation (Brown et al., 2003; Magistretti et al., 1993; Wyss et al., 2011). The importance of astrocyte-to-neuron lactate transport has been demonstrated by the recent report demonstrating that IOX1 it is required for long-term memory formation in vivo (Suzuki et al., during 2011). Although astrocytes can release lactate in response to glutamate uptake (Magistretti, 2006; Magistretti et al., 1999; Wender et al., 2000), here we describe another molecular pathway that leads to glycogen metabolism and lactate efflux as a result of metabolic

or neuronal activity. Soluble adenylyl cyclase (sAC) is sensitive to bicarbonate (HCO3−) and is posited to be a metabolic sensor (Zippin et al., 2001); however, its cellular distribution and function in the brain have not been identified. Due to their relationship to pH, HCO3− and HCO3−-sensitive enzymes represent a potentially effective way by which cells can initiate cellular cascades to meet metabolic demands that are often accompanied by changes in acid/base homeostasis. HCO3−-mediated sAC activation increases the production of the second messenger cAMP (Chen et al., 2000). In astrocytes, high levels of cAMP lead to the breakdown of glycogen (Sorg and Magistretti, 1992) and the production of lactate that can serve as an alternative energy source to neurons. Thus, new enzymes that lead to cAMP generation in astrocytes may be critical for mobilizing metabolic support for neurons during periods of intense neural activity or glucose deprivation.

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