Divalent cations and the activation kinetics of potassium channels in squid giant axons.

Abstract

A B ST RA C T The effects of external Zn +2 and other divalent cations on K channels in squid giant axons were studied. At low concentration (2 mM) Zn +2 slows opening kinetics without affecting closing kinetics . Higher concentrations (5-40 mM) progressively slow opening and speed channel closing to a lesser degree. In terms of "shifts," opening kinetics are strongly shifted to the right on the voltage axis, and OFF kinetics much less so . The shift of the conductancevoltage relation along the axis is intermediate . Zinc's kinetic effects show little sign of saturation at the highest concentration attainable . Zn does not alter the shape of the instantaneous current-voltage relation of open channels . Some other divalent cations have effects similar to Zn+2, Hg2+ being the most potent and Ca 12 the least. After treatment with H g+2, which is irreversible, Zn +2 still slows opening kinetics, which suggests that each channel has at least two sites for divalent cation action . The results are not compatible with a simple theory of fixed, uniform surface charges. They suggest that external cations interact directly with a negatively charged element of the gating apparatus that moves inward from the membrane's outer surface during activation . Examination of normal kinetics shows that there is a slow step somewhere in the chain leading to channel opening, but the slowest step must not be the last one.

Identification and Functional Characterization of a K+Channel α-Subunit with Regulatory Properties Specific to Brain

“…The formation of heteromultimeric channels by the Kv2.1/Kv2.3r dimer also was evaluated by studying its sensitivity to external Zn 2ϩ . The activity of many K ϩ channels is reduced by externally applied Zn 2ϩ (see Gilly and Armstrong, 1982). However, it is known that the Kv2.1 channels are rather insensitive to the cation, with a Kd value of 14 mM (De Biasi et al, 1993).…”

Inhibition of delayed rectifier K+‐current by levcromakalim in single intestinal smooth muscle cells: effects of cations and dependence on K+‐flux

“…In this study we have extended this approach, investigating the effects of Ba2", Zn* and Rb+, cations which might be expected to interact in or near K channel pore regions Gilly & Armstrong, 1982;Kwok & Kass, 1993; see also Hille, 1992). As a result we have found marked differences in the properties of the levcromakalim-induced and delayed rectifier K-currents.…”

Chemical modification of potassium channel gating in frog myelinated nerve by trinitrobenzene sulphonic acid.

“…Fig. 14A shows a one barrier energy diagram representing this mechanism, analogous to those used to describe the effects of adrenaline, pH and divalent cations on K channel gating (Tsien, 1974;Shrager, 1974;Gilly & Armstrong, 1982 following TNBS treatment. Changing the barrier height, G02, changes both opening and closing rate constants and therefore cannot reproduce the effects of TNBS.…”