Voltage-gated potassium channels

Publisher Summary This chapter discusses the molecular biology of voltage-activated K (K v ) channels. Three types of K v channel inactivation have been described in molecular terms: N-type, P-type, and C-type inactivation. N-type inactivation is linked to the presence of an amino-terminal inactivating domain, P-type inactivation to the presence of certain amino acid side-chains within the pore, and C-type inactivation depends on residues in S6. N-type inactivation refers to a rapid inactivation of K v channels via an amino (N)-terminal inactivating domain. Studies propose that N-type inactivation may operate in a ball-and-chain type mechanism. The amino-terminus would behave like a tethered ball that swings upon depolarization of the membrane into the K v channel pore and occludes it from the inside. Studies also show that deletion of amino-terminal inactivating domains leads to a loss of N-type inactivation. The inactivating domain can be added in the form of a peptide back to inside-out patches containing K v channels. This leads to a rapid inactivation of otherwise non-inactivating K v channels. The biological significance of K v channel diversity may be related to their widely varying functions in controlling cellular signal transduction, secretion, and (or) cell proliferation. In the nervous system, K v channels are involved in the regulation and control of action potential waveforms and frequencies, thresholds of excitation, setting the resting potential, and attenuation of cell excitability. Thus, the expression of different K v channels may aid the complex nervous system in encoding distinct pre- and post-synaptic signals that is required in the specific spatial and temporal integration of synaptic inputs and in the firing of correspondent output signals.