FUNCTIONAL DIFFERENCES OF A K(V)2.1 CHANNEL AND A K(V)2.1 K(V)1.2S4-CHIMERA ARE CONFINED TO A CONCERTED VOLTAGE SHIFT OF VARIOUS GATING PARAMETERS/

When expressed in Xenopus oocytes, the voltage-dependent K+ channels K (v)1.2 and K(v)2.1 have similar steady state parameters of activation but the kinetics of activation is significantly faster in the K(v)1.2 channels. Activation results from intramolecular arrangements which st art with the movement of the voltage sensor and end with the opening o f the pore, The S4-segment and the HS-loop comprise at least parr of t he respective involved structural elements. The molecular mechanism of coupling between sensing of voltage and opening of the pore is less w ell understood, We have measured whole cell and single channel ionic c urrents in the rapidly activating K(v)1.2 channel of the rat, the slow ly activating K(v)2.1 channel of the human, and in an S4-chimera K(v)2 .1/K(v)1.2S4. With respect to the K(v)2.1 channel, steady state activa tion and steady state C-type inactivation of the chimeric channel are shifted by more than 50 mV in the depolarizing direction. The property of rapid activation in K(v)1.2 channels was not transferred to the K( v)2.1 channels with the transplanted S4-region. Instead, the kinetics of activation, deactivation, and recovery from C-type inactivation as well as the voltage sensitivity of the 4-aminopyridine block are simil ar to the corresponding processes in K(v)2.1 channels if they are I-el ated to the steady state activation and inactivation, respectively. Th e unitary current and the mean open time of single channel openings of the S4-chimeric channels resemble the respective values of K(v)2.1 ch annels. It is concluded that the insertion of the S4-segment of K(v)1. 2 channels into K(v)2.1 channels modifies the gating at the early step s of activation leaving all properties associated with the open state( s) of the K(v)2.1 channels unaffected.