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Inhibition of delayed rectifier K + conductance in cultured rat cerebellar granule neurons by activation of calcium‐permeable AMPA receptors
Author(s) -
Jones Glyn,
Boyd David F.,
Yeung Shuk Yin,
Mathie Alistair
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00983.x
Subject(s) - ampa receptor , kainate receptor , cnqx , chemistry , biophysics , sgk1 , glutamate receptor , receptor , biochemistry , biology , kinase
Activation of AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid) receptors in cerebellar granule cells during perforated‐patch whole‐cell recordings activated an inward current at negative voltages which was followed, after a delay, by the inhibition of an outward potassium current at voltages positive to −20 mV. The activated inward current was inwardly rectifying suggesting that the AMPA receptors were Ca 2+ ‐permeable. This was confirmed by direct measurements of intracellular calcium where Ca 2+ rises were seen following AMPA receptor activation in Na + ‐free external solution. Ca 2+ rises were equally large in the presence of 100 μ m Cd 2+ to block voltage‐gated Ca 2+ channels. Specific voltage‐protocols, allowing selective activation of the delayed rectifier potassium current (K V ) and the transient A current (K A ), showed that kainate inhibited K V , but not to any great extent K A . The inhibition of K V was blocked by the AMPA receptor antagonist CNQX (6‐cyano‐7‐nitroquinoxaline‐2,3‐dione) and was no longer observed when the K V current was abolished with high concentrations of Ba 2+. The responses to kainate were not altered by pre‐treating the cells with pertussis toxin, suggesting that the AMPA receptor stimulation of the G‐protein G i cannot account for the effects observed. Replacing extracellular Na + with choline did not alter the inhibition of K V by kainate, however, removing extracellular Ca 2+ reduced the kainate response. The inhibition of K V by kainate was unaffected by the presence of 100 μ m Cd 2+. The guanylyl cyclase inhibitor, ODQ (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one), did not alter kainate inhibition of K V . It is concluded that ion influx (particularly Ca 2+ ions) through AMPA receptor channels following receptor activation leads to an inhibition of K V currents in cerebellar granule neurons.