Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit.
Within auditory pathways, the intrinsic electrical properties of neurons, and in particular their complement of potassium channels, play a key role in shaping the timing and pattern of action potentials produced by sound stimuli. The Kv9.1 gene encodes a potassium channel alpha subunit that is expressed in a variety of neurons, including those of the inferior colliculus. When cRNA encoding this subunit is injected into Xenopus oocytes, no functional channels are expressed. When, however, Kv9.1 is co-expressed with certain other alpha potassium channel subunits, it changes the characteristics of the currents produced by these functional channel proteins. We have found that Kv9.1 isolated from a rat brain cDNA library alters the kinetics and the voltage-dependence of activation and inactivation of Kv2.1, a channel subunit that generates slowly inactivating delayed rectifier potassium currents. The rate of activation of Kv2.1 is slowed by co-expression with Kv9.1. With Kv2.1 alone, the amplitude of evoked currents increases monotonically with increasing command potentials. In contrast, when Kv2.1 is co-expressed with Kv9.1, the amplitude of currents increases with increasing depolarization up to potentials of only approximately +60 mV, after which increasing depolarization results in a decrease in current amplitude. Currents produced by Kv2. 1 alone and by Kv2.1/Kv9.1 are both sensitive to the potassium channel blocker tetraethyl ammonium ions (TEA), but higher concentrations of TEA (20 mM) eliminate the biphasic voltage-dependence of the Kv2.1/Kv9.1 currents. Co-expression with Kv9.1 also produces an apparent negative shift in the voltage-dependence of inactivation and activation. Computer simulations of model neurons suggest that co-expression of Kv9.1 with Kv2.1 may have different effects in neurons depending on whether their firing pattern is limited by the inactivation of inward currents. In excitable cells in which the inward currents do not inactivate, co-expression with Kv9.1 could produce an inhibition of firing during sustained depolarization. In contrast, in model neurons with rapidly inactivating inward current, the change in the voltage-dependence of activation produced by Kv9.1 may allow the cells to follow high frequency stimulation more effectively.
Richardson
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Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Kaczmarek
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LK
D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels; D005072:Evoked Potentials, Auditory; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051669:Shab Potassium Channels; D014982:Xenopus laevis
D051668:Delayed Rectifier Potassium Channels; C496988:KCNB1 protein, human; C503456:KCNS1 protein, human; C496991:Kcnb1 protein, rat; C503465:Kcns1 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels