Ion–Ion Interactions at the Selectivity Filter

نویسندگان

  • David Immke
  • Stephen J. Korn
چکیده

In the Kv2.1 potassium channel, binding of K(+) to a high-affinity site associated with the selectivity filter modulates channel sensitivity to external TEA. In channels carrying Na(+) current, K(+) interacts with the TEA modulation site at concentrations </=30 microM. In this paper, we further characterized the TEA modulation site and examined how varying K(+) occupancy of the pore influenced the interaction of K(+) with this site. In the presence of high internal and external [K(+)], TEA blocked 100% of current with an IC(50) of 1.9 +/- 0.2 mM. In the absence of a substitute permeating ion, such as Na(+), reducing access of K(+) to the pore resulted in a reduction of TEA efficacy, but produced little or no change in TEA potency (under conditions in which maximal block by TEA was just 32%, the IC(50) for block was 2.0 +/- 0.6 mM). The all-or-none nature of TEA block (channels were either completely sensitive or completely insensitive), indicated that one selectivity filter binding site must be occupied for TEA sensitivity, and that one selectivity filter binding site is not involved in modulating TEA sensitivity. At three different levels of K(+) occupancy, achieved by manipulating access of internal K(+) to the pore, elevation of external [K(+)] shifted channels from a TEA-insensitive to -sensitive state with an EC(50) of approximately 10 mM. Combined with previous results, these data demonstrate that the TEA modulation site has a high affinity for K(+) when only one K(+) is in the pore and a low affinity for K(+) when the pore is already occupied by K(+). These results indicate that ion-ion interactions occur at the selectivity filter. These results also suggest that the selectivity filter is the site of at least one low affinity modulatory effect of external K(+), and that the selectivity filter K(+) binding sites are not functionally interchangeable.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel.

Ion selectivity is critical for the biological functions of voltage-dependent cation channels and is achieved by specific ion binding to a pore region called the selectivity filter. In voltage-gated K+, Na+ and Ca2+ channels, the selectivity filter is formed by a short polypeptide loop (called the H5 or P region) between the fifth and sixth transmembrane segments, donated by each of the four su...

متن کامل

K(+) versus Na(+) ions in a K channel selectivity filter: a simulation study.

Molecular dynamics simulations of a bacterial potassium channel (KcsA) embedded in a phospholipid bilayer reveal significant differences in interactions of the selectivity filter with K(+) compared with Na(+) ions. K(+) ions and water molecules within the filter undergo concerted single-file motion in which they translocate between adjacent sites within the filter on a nanosecond timescale. In ...

متن کامل

Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter.

The chromanol 293B (293B, trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman) is a lead compound of potential class III antiarrhythmics that inhibit cardiac I(Ks) potassium channels. These channels are formed by the coassembly of KCNQ1 (Kv7.1, KvLQT1) and KCNE1 subunits. Although homomeric KCNQ1 channels are the principal molecular targets, entry of KCNE1 to the chan...

متن کامل

Ion Selectivity in the Selectivity Filters of Acid-Sensing Ion Channels

Sodium-selective acid sensing ion channels (ASICs), which belong to the epithelial sodium channel (ENaC) superfamily, are key players in many physiological processes (e.g. nociception, mechanosensation, cognition, and memory) and are potential therapeutic targets. Central to the ASIC's function is its ability to discriminate Na(+) among cations, which is largely determined by its selectivity fi...

متن کامل

Selectivity filter gate versus voltage-sensitive gate: A study of quantum probabilities in the Hodgkin-Huxley equation

The Hodgkin-Huxley (HH) model is a powerful model to explain different aspects of spike generation in excitable cells. However, the HH model was proposed in 1952 when the real structure of the ion channel was unknown. It is now common knowledge that in many ion-channel proteins the flow of ions through the pore is governed by a gate, comprising a so-called ”selectivity filter” inside the ion ch...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of General Physiology

دوره 115  شماره 

صفحات  -

تاریخ انتشار 2000