High-order intersubunit coupling pattern of the Shaker tandem tetrameric Kv channel is consistent with a concerted all-or-none activation gate-opening transition. (A) Pairwise intersubunit coupling free energies (Δ2Gi,j) of the six possible i,j subunit pairs. (B) Comparison of the second-, third-, and forth-order intersubunit coupling free energies associated with the subunit pairs indicated in A. Third- and fourth-order intersubunit coupling energies (Δ3G(i,j)k and Δ4G(i,j)(k,l), respectively) represent the effect of a third (k) subunit or interacting subunit pair (k,l) on the magnitude of coupling between an adjacent i,j subunit pair.