TY - JOUR
T1 - Gating dependence of inner pore access in inward rectifier K+ channels
AU - Phillips, L. Revell
AU - Enkvetchakul, Decha
AU - Nichols, Colin G.
N1 - Funding Information:
This work was supported by grants HL54171 (to C.G.N.) and DK60086 (to D.E.) from the NIH and by the NIH Biophysical Training Grant at Washington University. We are also grateful to the Washington University Diabetes Research and Training Center for reagent support.
PY - 2003/3/27
Y1 - 2003/3/27
N2 - Cation channel gating may occur either at or below the inner vestibule entrance or at the selectivity filter. To differentiate these possibilities in inward rectifier (Kir) channels, we examined cysteine accessibility in the ATP-gated Kir6.2 channel. MTSEA and MTSET both block channels and modify M2 cysteines with identical voltage dependence. If entry is restricted to open channels, modification rates will slow in ATP-closed channels, but because the reagent can be trapped in the pore following brief openings, this may not be apparent until open probability is extremely low (<0.01). When these conditions are met, modification does slow significantly, indicating gated access and highlighting an important caveat for interpretation of MTS-accessibility measurements: reagent "trapping" in nominally "closed" channels may obscure gated access.
AB - Cation channel gating may occur either at or below the inner vestibule entrance or at the selectivity filter. To differentiate these possibilities in inward rectifier (Kir) channels, we examined cysteine accessibility in the ATP-gated Kir6.2 channel. MTSEA and MTSET both block channels and modify M2 cysteines with identical voltage dependence. If entry is restricted to open channels, modification rates will slow in ATP-closed channels, but because the reagent can be trapped in the pore following brief openings, this may not be apparent until open probability is extremely low (<0.01). When these conditions are met, modification does slow significantly, indicating gated access and highlighting an important caveat for interpretation of MTS-accessibility measurements: reagent "trapping" in nominally "closed" channels may obscure gated access.
UR - http://www.scopus.com/inward/record.url?scp=0037468788&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(03)00155-7
DO - 10.1016/S0896-6273(03)00155-7
M3 - Article
C2 - 12670424
AN - SCOPUS:0037468788
SN - 0896-6273
VL - 37
SP - 953
EP - 962
JO - Neuron
JF - Neuron
IS - 6
ER -