Mechanism of ion permeation through calcium channels

Abstract

Calcium channels carry out vital functions in a wide variety of excitable cells but they also face special challenges. In the medium outside the channel, Ca2+ ions are vastly outnumbered by other ions. Thus, the calcium channel must be extremely selective if it is to allow Ca2+ influx rather than a general cation influx. In fact, calcium channels show a much greater selectivity for Ca2+ than sodium channels do for Na+ despite the high flux that open Ca channels can support. Relatively little is known about the mechanism of ion permeation through Ca channels. Earlier models assumed ion independence or single-ion occupancy. Here we present evidence for a novel hypothesis of ion movement through Ca channels, based on measurements of Ca channel activity at the level of single cells or single channels. Our results indicate that under physiological conditions, the channel is occupied almost continually by one or more Ca2+ ions which, by electrostatic repulsion, guard the channel against permeation by other ions. On the other hand, repulsion between Ca2+ ions allows high throughput rates and tends to prevent saturation with calcium.

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

“…The data are confirmed by independent calculations (lines in Fig. 5; equation after Hess & Tsien, 1984) implying one cation-binding site for the ion channel I and a monotonic function for the current in Ca+Mg. The Km Mg value (7 x 10-4 M), used for the calculations (Fig.…”

“…5 represent calculations obtained independently from the measured data points using the equation in the legend of Fig. 5 (Hess & Tsien, 1984 Inward current II was always reduced upon the addition of Mg to a Ca-containing solution (data not shown) and declined below the value in Ca-only solution. The more Mg added, the more current II was suppressed (compare Fig.…”

From Structure to Function in Open Ionic Channels

“…The AMFE of L-type calcium channels has received a great deal of attention (e.g., Almers & McCleskey, 1984;Almers, Palade & McCleskey, 1984;Armstrong & Neyton, 1992;Chen, Bezprozvanny & Tsien, 1996;Dang & McCleskey, 1998;Heinmann et al, 1992;Hess, Lansman & Tsien, 1986;Hess & Tsien, 1984;Lee & Tsien, 1983;Tsien et al, 1987). Indeed, it is probably not an exaggeration to say that the properties of these channels have formed the paradigm (Almers & McCleskey, 1984;Hess & Tsien, 1984;Hille, 1975;Hille, 1992) taught to most students of permeation for nearly twenty years. Thus, it is important to see whether PNP can account for this data.…”

“…When reading the literature of calcium channels, it is important to realize that the data on the L-type calcium channel (Almers & McCleskey, 1984;Hess & Tsien, 1984) do not establish the existence of an AMFE in conductance, but rather describe a complex concentration dependence of current, that might be called a mole fraction effect MFE, to distinguish it from the AMFE of conductance. The distinction between current and conductance is not purely semantic; it has been as central to channology since 1952 as it has been to the physics of electricity since 1826 when…”

Amphiphilic Blockers Punch through a Mutant CLC-0 Pore

“…In some examples, however, blockers can permeate through channel pores. Divalent cations, for example, can block the voltage-gated Ca 2+ channel by obstructing the current carried by monovalent cations ( Almers et al, 1984 ;Hess and Tsien, 1984 ). However, the voltage-gated Ca 2+ channel allows Ca 2+ ions to permeate through the pore, and it is the infl ux Ca 2+ ions that mediate numerous important physiological functions.…”