Hypokalemic periodic paralysis (HypoPP) is a hereditary neurologic disorder caused by point mutations in the muscular voltage-gated calcium (HypoPP-1) or sodium (HypoPP-2) channel genes. In this study, we heterologously expressed the wild-type and HypoPP-1 mutations introduced at the corresponding sites in the rabbit cardiac calcium channel in HEK-293 cells (R650H, R1362H, R1362G). Additionally, to estimate the cooperative effects of the HypoPP-1 mutations on channel gating, we expressed two double mutants (R650H/R1362H, R650H/R1362G). Data were obtained by whole-cell patch-clamp technique and analysed by a global fitting procedure whereby several current traces elicited by different potentials were simultaneously fit to the kinetic model containing four closed, two open (O1 and O2) and two inactivated states. We found that all HypoPP-1 mutations have loss-of-function features: D4/S4 mutants shift the equilibrium to the closed states which results in reduced open probability, shorter openings and, therefore, in smaller currents, and the D2/S4 mutant slows the activation. Additionally, HypoPP-1 histidine mutants favored the second open state O2. As O2 was suggested to be less selective for divalent cations, the re-distribution of the open states towards O2 in HypoPP-1 may produce leaky calcium channels, which permeate Na+ ions, causing membrane depolarization, reduced action potentials and paralysis.