Potassium channels as multi-ion single-file pores.

Abstract

a B S TRAC T A literature review reveals many lines of evidence that both delayed rectifier and inward rectifier potassium channels are multi-ion pores. These include unidirectional flux ratios given by the 2-2.5 power of the electrochemical activity ratio, very steeply voltage-dependent block with monovalent blocking ions, relief of block by permeant ions added to the side opposite from the blocking ion, rectification depending on E -EK, and a minimum in the reversal potential or conductance as external K + ions are replaced by an equivalent concentration of TI + ions. We consider a channel with a linear sequence of energy barriers and binding sites. The channel can be occupied by more than one ion at a time, and ions hop in single file into vacant sites with rate constants that depend on barrier heights, membrane potential, and interionic repulsion. Such multi-ion models reproduce qualitatively the special flux properties of potassium channels when the barriers fi~r hopping out of the pore are larger than for hopping between sites within the pore and when there is repulsion between ions. These conditions also produce multiple maxima in the conductance-ion activity relationship. In agreement with Armstrong's hypothesis (1969.J. Gen. Physiol. 54:553-575), inward rectification may be understood in terms of block by an internal blocking cation. Potassium channels must have at least three sites and often contain at least two ions at a time.Evidence has accumulated, for the sodium channel and for several types of potassium channels of electrically excitable cells, that ions interact with the channel and with other ions in it while diffusing across the membrane (French and Adelman, 1976). An earlier paper of Hille (1975 b) discussed a model of the sodium channel in which the permeating ion must pass across a sequence of four energy barriers to cross the membrane. Inasmuch as the model assumed that no more than one ion could be in the channel at a time, it was called a oneion pore. In this paper we consider a similar type of linear, multibarrier model for a multi-ion pore where more than one ion may be in a channel at a time, and the ions are not permitted to pass by each other as they move through the channel. These assumptions lead to phenomena commonly referred to as "single-file diffusion" or the "long pore effect" which have been reported in measurements of the passive movement of ions in potassium channels of nerve, muscle, and other cell membranes. Our goal is to show that the major transport properties of potassium channels may be accounted for by this class of multi-ion channel models. For practical reasons, only a qualitative agreement is demonstrated here. An attempt to make more realistic models would need many more J. GEN. PHYSIOL. 9 The Rockefeller University Press .

A conductance maximum observed in an inward-rectifier potassium channel.

“…The theoretical basis for a reduction in conductance with increasing ion concentration has been discussed thoroughly in the literature (Hille and Schwarz, 1978;Kohler and Heckmann, 1979;Schumaker and MacKinnon, 1990). The effect is a direct consequence of a conduction mechanism where two or more ions diffuse (or hop from site to adjacent site) along a single-file pathway.…”

“…A fourth expected property of a channel that allows two or more ions to coexist along the conduction pathway is inhibition of conduction when the ion concentration is raised to sufficiently high levels on both sides of the membrane (Hille and Schwarz, 1978;Kohler and Heckmann, 1979;Schumaker and MacKinnon, 1990). Experimentally, the effect should be identifiable as a descending phase of the conductanceconcentration relationship at high ion concentrations.…”

Potentiation of EDHF-mediated relaxation by chloride channel blockers

“…Cl -channels are abundant in the vascular smooth muscle cells [31] and act as one of the major determinants of the membrane potential. Theoretically, a change in Cl -conductance may influence the activity of other voltage-sensitive channels or transporters [32] . As shown in the present study, the potentiating effects of Cl -channel blockers on K + -induced relaxations were only reversed by K ir channel blocker BaCl 2 , but not by Na + /K + -ATPase inhibitor ouabain.…”

“…It is hitherto contradictory whether or not the Na + ,K + -ATPase is voltage-dependent [1,11] . However, K ir channels have been proved to be voltage-dependent [12] , which hyperpolarize cells by passing outward current in the voltage range just positive to the equilibrium potential of K + (E K ) [32] . It is known that the equilibrium potential of Cl -(E Cl ) is about 60 mV positive in relation to E K .…”

Different properties of two voltage‐dependent inward currents of the ciliate Stylonychia mytilus.

“…The reversal potential (3-6± 1-8 mV, n = 10) of the mechanosensitive receptor current in 1 mM-Mg was measured by de Peyer & Deitmer (1980). Those (Hagiwara, Miyazaki, Moody & Tatlak, 1978;Hille & Schwarz, 1978). In Stylonychia, Ba+Ca was used to investigate inward current II (Ballanyi & Deitmer, 1984).…”