Persistent Sodium Channel

Persistent Sodium Channel - High Conductance Sustained...

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High Conductance Sustained Single-Channel Activity Responsible for the Low-Threshold Persistent Na+ Current in Entorhinal Cortex Neurons Mark Bluemke, Dan Schuster Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455 (21 September 2007)
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Purpose: The experiments in this paper were performed to help better understand the Na+ channels responsible for persistent current (I NaP ) in EC stellate cells Why strive to further understand these persistent currents? *These currents contribute to oscillatory potentials. What’s the significance of this? **The stellate cells of layer II (ECIIscs) play an important part in the genesis of the theta rhythm. These neurons occupy a key position in the neocortex- hippocampus-neocortex circuit, a crucial crossroad in memory functions. **Oscillatory potentials may also play a role in temporal lobe eptilogensis
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Copyright ©1999 The American Physiological Society Pedroarena, C. M. et al. J Neurophysiol 82: 1465-1476 1999 Fig. 1. C : example of recordings obtained from the neuron shown in B that exhibited "spontaneous " membrane potential oscillations on penetration by the microelectrode. - - -, membrane potential value (52 mV) during brief pauses of the oscillations. Note the characteristic AM of the oscillations. Oscillatory waves were composed of brief depolarizing and hyperpolarizing phases. Mesencephalic trigeminal sensory neurons
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Copyright ©1999 The American Physiological Society Pedroarena, C. M. et al. J Neurophysiol 82: 1465-1476 1999 Fig. 9. TTX was the only drug administered that abolished the oscillatory activity Indicates those responsible are TTX sensitive Na+ channels K+ channel blockers (TEA, 4- AP, and intracellular Cs ions)
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Hypotheses of I NaP generation: •Caused by rare, short-lived transitions of conventional transient Na+ channels to a slowly inactivating mode •Caused by distinct transient and persistent channel isoforms •Single channels mediate both activities by means of – channel kinetics and conductance regulated by phosphorylation, auxiliary subunits, or some other type of long lasting modulation •Predisposition to persistent gating, others more dedicated to transient gating
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Methods – Cell Preparations Brains from male Long-Evans rats at P25 400uM slices cut in ice cold dissociation buffer (in mM: 115 NaCl, 3 KCl, 3 MgCl 2 , 0.2 CaCl 2 , 25 glucose, 20 PIPES) Layer II of entorhinal cortex dissected out and placed in dissociation buffer at 32 o C Incubated with Protease type XIV (non-specific) for 15 minutes Washed and left at room temperature Cell separation completed via trituration through Pasteur pipettes with progressively smaller tips
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This note was uploaded on 04/07/2008 for the course NSCI 5461 taught by Professor Newman during the Spring '08 term at Minnesota.

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Persistent Sodium Channel - High Conductance Sustained...

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