For many potassium channels, tetramerization domains in either N- or C-terminal of the pore domain assist in tetramer assembly by increasing local concentrations of monomeric subunits. However, the structure of the pore domain as a monomer before tetramerization is not clear. Recently, thiol-labeling experiments have shown that isolated monomers engineered from the voltage-gated potassium channel Kv1.3 can readily adopt their native fold as they are being synthesized. Mutations at certain critical positions make the p-helix become more solvent-exposed; however, the mechanism by how the p-helix becomes more solvent-exposed is unclear. Here, our MD simulations and NMR measurements to show that the monomeric pore domains of potassium channels are heterogeneous and dynamic. According to the simulations, WT Kv1.2 monomer is unstable in its native-like structure and the 3 helices are very dynamic in the membrane. While the 3 helices separate from each other and form many non-native interactions, all helices retain their helical structure and remain buried in the membrane. Simulations of mutants (W384A/W385A/V387E, V387E, and V388E) also show the separation of all 3 helices, yet the p-helix loses helicity and becomes less stable, leading to higher solvent-exposure of the p-helix. We found that the helicity and membrane burial of the p-helix depends on the locations of the inserted charged groups. When a charged group is introduced to the opposite face of the helix as the native aspartate D381, the p-helix leaves the membrane and loses its helicity but when the mutation is on the same face, the helix goes into the interfacial region and retains its helical nature. In addition, our NMR spectroscopy and hydrogen exchange measurements suggest that the WT monomer of KcsA in lipid bicelles may be highly heterogeneous, but are all buried in the membrane. Together, we suggest that the WT monomers are highly dynamic before tetramerization and the locations of mutations on the p-helix highly dictate its helicity and burial.