Although AMPA receptor subunit configuration controls the Ca2+ permeability of the ion channel, not much is known about Ca2+ signals generated by different AMPA receptor subtypes. We examined the Ca2+ signaling properties of recombinant AMPA receptors using patch clamp to determine ionic permeability properties and Ca2+ imaging to examine changes in intra-cellular Ca2+ level ([Ca2+]i). Activation of recombinant AMPA receptors robustly increased [Ca2+]i even in cells expressing heteromeric receptors containing edited GluRB, which harbored receptors with very low average Ca2+ permeability in patch clamp studies. The results suggest that whereas the GluRB subunit controls Ca2+ permeability, Ca2+ signaling mediated by AMPA receptors correlates poorly with the presence of GluRB.