What keeps Kv channels small? The molecular physiology of modesty

C o m m e n t a r y All known K + channels use the same molecular architecture to achieve K + selectivity. Selectivity filters, even from distantly related K + channels, appear nearly identical in atomic resolution crystal structures; remarkably, the deviation in the coordinates of K +-coordinating backbone carbonyls is less than the uncertainty in the mod-Brohawn et al., 2012). Although retaining an exquisite selectivity for K + , this highly conserved filter allows passage of a significant flux of ions. The large conductance calcium-activated K + channel (also known as Big Potassium , BK, Maxi-K, KCNMA1, and Slo1) has a single-channel conductance near 300 pS at physiological K + concentrations, or >500 pS in saturating [K + ] (Brelidze and Magleby, 2004). Most other K + channels have markedly lower conductances, and none of the mammalian voltage-gated (Kv) family of K + channels has a conduc-tance approaching that of BK (Gutman et al., 2005). Given the extreme conservation of the selectivity filter structure among K + channels, it is likely that the selectiv-ity filters of all K + channels are capable of such flux. In fact, numerous point mutations distal to the selectivity filter can increase the unitary conductance of Kv channels (Lopez et al., 1994; Sukhareva et al., 2003). It would appear that nature has governed the conductance of these channels, muffling their thunderous flux. In this issue, Díaz-Franulic et al. in David Naranjo's laboratory systematically assess how physical and chemical determinants outside of the selectivity filter govern conduc-tance of a Kv channel. The article " Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels " addresses a fundamental biophysical question: What physical features of Shaker's inner cavity limit ionic flux? To investigate this question, the authors measured unitary conductance while using three biochemical perturbations: adding sugar, adding K + , and electrostatically charging the channel's inner cavity. Sugar Díaz-Franulic et al. (2015) measured the effects of sucrose-induced viscosity changes on channel conductance. Increasing sucrose concentration enables measurement Correspondence to Jon T. Sack: j s a c k @ u c d a v i s. e d u of the resistance of different segments in the permeation path (Brelidze and Magleby, 2005). This perturbation slows the diffusion of K + , essentially by getting in their way, such that diffusion is retarded. The effect of sucrose on diffusion …