Modification of rat brain Kv1.4 channel gating by association with accessory Kvβ1.1 and β2.1 subunits

Abstract

We have examined the effects of co-expression of Kvbeta1.1 and Kvbeta2.1 subunits on the gating of rat brain Kv1.4 channels, expressed in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating "A" type current, which activated at potentials beyond -60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements were fitted with a Boltzmann function, with V1/2 = -47 mV and k = 10 mV. Neither the Kvbeta1.1 nor Kvbeta2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvbeta2.1 subunit, which lacks an N-terminal inactivation domain, was almost as effective as the Kvbeta1.1 subunit in speeding up Kv1.4. Steady-state inactivation of Kv1.4 was unchanged upon co-expression with either Kvbeta1.1 or Kvbeta2.1 subunits. Kv1.4 recovered from inactivation with two time constants; apart from an approximately 50% lengthening of the slow time constant with a high Kvbeta2.1 injection ratio, neither time constant was altered by either the Kvbeta1.1 or Kvbeta2.1 subunits, suggesting little interaction with recovery from C-type inactivation. Clearly, beta subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested previously.

Subunit Composition of Kv1 Channels in Human CNS

“…The expression of Kvβ3 mRNA is prominent only in the olfactory bulb and thalamic nuclei (Heinemann et al, 1995) ; thus, it is unlikely to be found in these samples. The auxiliary subunits have distinct functions : Kvβ1 confers rapid inactivation on noninactivating α subunits (Rettig et al, 1994 ; Heinemann et al, 1996), and Kvβ2.1 behaves as a chaperone for Kv1.2 (Rhodes et al, 1996) and modifies the gating of Kv1.4 (McCormack et al., 1995 ; McIntosh et al, 1997). It also affects the Kvβ1.1‐mediated K + ‐current inactivation (Xu and Li, 1997).…”

Characteristics of Brain Kv1 Channels Tailored to Mimic Native Counterparts by Tandem Linkage of α Subunits

“…K ϩ currents were recorded after 72 h, using a two-microelectrode voltage clamp amplifier (TEC-03; NPI) as described previously (26) during voltage steps to ϩ20 mV from a holding potential of Ϫ80 mV. DTX k was applied by superfusion (at a rate of 5 ml/min), and its concentration increased cumulatively.…”

Multiple Modes of A-Type Potassium Current Regulation

“…Thus, Kv 1 and Kv 3 subunits interact with the Kv1 family ofsubunits and induce rapid inactivation in all Kv1 channels [7,10,27,28], except Kv1.6 that has a NIP-an N-type inactivation prevention domain [29]. Kv 2 has no inactivation ball therefore it does not convert their partners into A-type channels although it can accelerate inactivation kinetics [30]. Generally, the -ball and theball do not have direct interactions [31] although they may share sequence homology as, for instance, the -balls of Kv 1 and Kv 3 with the -balls of Kv1.4 and Kv3.4.…”