Activation Gating of Potassium Channel Pores: A Unified Mechanism?

BSF grant: Activation gating of potassioum channel pore: A unified mechanism?Summary of achivements This summary is mainly based on a paper entitled 'Inverse coupling in leak and voltage-activated K+ channel gates underlies distinct roles in electrical signaling' published in Nature Structural and Molecular Biology in 2009.

Voltage-activated (Kv) and leak (K2P) potassium channels play key and distinct roles in electrical signaling in the nervous system. During the grant period we examined how differences in the operation of the activation and slow inactivation pore gates of Kv and K2P channels underlie their distinct roles in electrical signaling. We found out that: (1) a lower activation gate exists also in the leak potassium channel family.

(2) that the activation gate is an important determinant in controlling intrinsic conformational stability of the the K+ channel pore.

(3) that the lower activation and upper slow inactivation gates of leak channels crosstalk.

(4) and that, in contrast to Kv channels where the two pore gates are negatively coupled, i.e. that the opening of the lower activation gate stimulates the closure of the upper slow inactivation gate, for K2P channels the two gates are positively coupled.

Our results suggest how differences in basic thermodynamic pore properties, in particular intrinsic conformational stability and modes of coupling between activation and inactivation gates (a thermodynamic linkage relation), underlie the distinct roles Kv and leak K+ channels play in electrical signaling.