Kv1.4 channels are voltage-gated potassium channels which produce a rapidly inactivating current, which is thought to be the molecular basis of the transient outward current seen in the endocardium of several mammalian species. Kv1.4 channels exhibit two distinct inactivation mechanisms. Fast “N-type” inactivation is well characterized, and operates by a “ball and chain” mechanism. The slower C-type inactivation is not so well defined, but involves conformational changes of the pore resulting in a block of current. We studied the interaction between these inactivation mechanisms using two electrode voltage clamp of Kv1.4 and Kv1.4ΔN (amino acids 2-146 deleted from the N-terminal to prevent N-type inactivation) cloned channels heterologously expressed in Xenopus oocytes. We manipulated C-type inactivation by altering extracellular potassium concentration and introducing a point mutation that diminishes C-type inactivation. We developed a computer model of Kv1.4ΔN (C-type inactivation) and Kv1.4 (N- and C-type inactivation) channels to determine the required degree of interaction between the inactivation mechanisms needed to replicate the experimental data. Using our four closed state model with distinct N- and C-type inactivated states, it was not possible to reproduce the experimental data without allowing direct transitions between the N- and C-type inactivated states. We examined this model in conjunction with a model of permeation and binding to potassium in the pore. The permeation model reproduces the conductance activity relationship of Kv1.4. In the context of inactivation/channel block, movement of potassium from the intracellular side of the channel to the outside cannot change occupancy of the external site when physiological levels of extracellular potassium are present. Changes in occupancy of the pore contribute only a small fixed energy in the presence of extracellular potassium. C-type inactivation is the rate-limiting step which determines recovery from inactivation, so understanding C-type inactivation, and how it is coupled to N-type inactivation is critical in understanding how a channel will act to repetitive stimulation in vivo. Our study suggests that N-type inactivation and, by similarity, open pore drug binding, interact with C-type inactivation primarily through an allosteric mechanism.