Abstract: Calcium channels in a variety of tissues may contain different subunits, including several different ? (gamma) subunits. We report studies regarding structural features of certain gamma subunits, for example the N-terminal first transmembrane domain (TM1) of the subunit ?6. We disclose that certain structural motifs, for example a GxxxG-like structural motif as described herein, can mediate subunit function for calcium channels. A particular peptide motif that has been identified as significant for the ability to mediate a decrease in calcium current is GxxxA. Compositions and methods are disclosed which are useful in modifying calcium regulation in mammalian cells. In various embodiments, calcium current is modified.