Modification of delayed rectifier potassium currents by the Kv9.1 potassium channel subunit

Within auditory pathways, the intrinsic electrical properties of neurons, a nd in particular their complement of potassium channels, play a key role in shaping the timing and pattern of action potentials produced by sound stim uli. The Kv9.1 gene encodes a potassium channel alpha subunit that is expre ssed in a variety of neurons, including those of the inferior colliculus. W hen cRNA encoding this subunit is injected into Xenopus oocytes, no functio nal channels are expressed. When, however, Kv9.1 is co-expressed with certa in other alpha potassium channel subunits, it changes the characteristics o f 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 s ubunit that generates slowly inactivating delayed rectifier potassium curre nts. 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-expresse d with Kv9.1, the amplitude of currents increases with increasing depolariz ation up to potentials of only similar to+60 mV, after which increasing dep olarization results in a decrease in current amplitude. Currents produced b y Kv2.1 alone and by Kv2.1/Kv9.1 are both sensitive to the potassium channe l blocker tetraethyl ammonium ions (TEA), but higher concentrations of TEA (20 mM) eliminate the biphasic voltage-dependence of the Kv2.1/Kv9.1 curren ts. Co-expression with Kv9.1 also produces an apparent negative shift in th e voltage-dependence of inactivation and activation. Computer simulations o f model neurons suggest that co-expression of Kv9.1 with Kv2.1 may have dif ferent effects in neurons depending on whether their firing pattern is limi ted 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 mo del neurons with rapidly inactivating inward current, the change in the vol tage-dependence of activation produced by Kv9.1 may allow the cells to foll ow high frequency stimulation more effectively. (C) 2000 Elsevier Science B .V. All rights reserved.