A region of the sulfonylurea receptor critical for a modulation of ATP-sensitive K+ channels by G-protein βγ-subunits

To determine the interaction site(s) of ATP‐sensitive K + (K ATP ) channels for G‐proteins, sulfonylurea receptor (SUR2A or SUR1) and pore‐forming (Kir6.2) subunits were reconstituted in the mammalian cell line, COS‐7. Intracellular application of the G‐protein βγ2‐subunits (G βγ2 ) caused a reduction of ATP‐induced inhibition of Kir6.2/SUR channel activities by lessening the ATP sensitivity of the channels. G βγ2 bound in vitro to both intracellular (loop‐NBD) and C‐terminal segments of SUR2A, each containing a nucleotide‐binding domain (NBD). Furthermore, a single amino acid substitution in the loop‐NBD of SUR (Arg656Ala in SUR2A or Arg665Ala in SUR1) abolished the G βγ2 ‐dependent alteration of the channel activities. These findings provide evidence that G βγ modulates K ATP channels through a direct interaction with the loop‐NBD of SUR.