The study reveals that K(IR)6.1 is not ATP-insensitive as previously believed, with ATP inhibiting hybrid channels at an IC50 of approximately 10^-5 m.
Challenges prior view of Kir6.1 ATP-insensitivity; leaves open relevance to native cardiovascular KATP channels.
K(IR)6.1 and K(IR)6.2 are the pore-forming subunits of K(NDP)(,) the nucleotide-diphosphate-activated K(ATP) channels, and classical K(ATP) channels, respectively. "Hybrid" channels, in which the structure is predetermined by concatemerizing K(IR)6.1 and K(IR)6.2, exhibit distinct conductivities specified by subunit number and position. Inclusion of one K(IR)6.2 is sufficient to open K(IR)6. X-X-X-X/SUR1(4) in the absence of nucleotide stimulation through sulfonylurea receptor-1 (SUR1). ATP inhibited the spontaneous bursting of hybrid channels with an IC(50(ATP)) approximately 10(-)(5) m, similar to that of K(IR)6.2(4)-containing channels. These findings and a transient increase in K(NDP) channel activity following rapid wash-out of MgATP suggested that K(IR)6.1 is not ATP-insensitive as previously believed. We propose that SUR-dependent, inhibitory ATP-enhanced interactions of the cytoplasmic domains of both K(IR)6.1 and K(IR)6.2 stabilize a closed form of the M2 bundle in the gating apparatus.
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Babenko et al. (2000) studied this question.
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