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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Characteristics of IA currents in adult rabbit cerebellar Purkinje cells.

Classical conditioning the rabbit nictitating membrane involves changes in synaptic and intrinsic membrane properties of cerebellar Purkinje cell dendrites, and a 4-aminopyridine (4-AP)-sensitive potassium channel underlies these membrane properties. We characterized I(A) currents in adult, rabbit Purkinje cells to determine whether I(A) is the target channel involved in learning. Whole-cell recordings of Purkinje cell somas and dendrites revealed a fast activating and inactivating current with half maximal activation at -27.08 +/- 3.48 mV and -25.51 +/- 1.15 mV in somas and dendrites, respectively; half maximal inactivation at -58.91 +/- 2.34 mV and -49.90 +/- 2.58 mV; and a recovery time constant of 22.81 +/- 1.92 ms and 16.60 +/- 4.26 ms. Outside-out patch recordings from cerebellar Purkinje cell somas confirmed these 4-AP-sensitive currents with half maximal activation at -13.85 +/- 1.17 mV and half maximal inactivation at -55.07 +/- 5.54 mV. More importantly, there was an overlap of activation and incomplete inactivation at potentials from -60 to -40 mV, suggesting a "window" current that was responsible for subthreshold variations of membrane potential and might underlie conditioning-specific increases in Purkinje cell excitability. The potassium current was inhibited by 4-AP and by Heteropodatoxin, a specific blocker of Kv4.2 and Kv4.3 channels, but not by Stromatoxin, a blocker of Kv4.2 channels. Mouse monoclonal antibody labeling identified both Kv4.3 and Kv4.2 subunits in the granule cell layer but only Kv4.3 subunits in the molecular layer. This is the first demonstration of A-type currents in adult, rabbit Purkinje cells that may play a role in regulating membrane potential and firing frequency and comprise the target channel mediating conditioning-specific changes of excitability in rabbit Purkinje cell dendrites.[1]


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