Expression and modulation of an invertebrate presynaptic calcium channel α1 subunit homolog

Here we report the first assessment of the expression and modulation of an invertebrate alpha(1) subunit homolog of mammalian presynaptic Ca(v)2 calcium channels ( N-type and P/Q-type) in mammalian cells. Our data show that molluscan channel (LCa(v)2a) isolated from Lymnaea stagnalis is effectively membrane-targeted and electrophysiologically recordable in tsA-201 cells only when the first 44 amino acids of LCav2a are substituted for the corresponding region of rat Ca(v)2.1. When coexpressed with rat accessory subunits, the biophysical properties of LCa(v)2a-5'rbA resemble those of mammalian N-type calcium channels with respect to activation and inactivation, lack of pronounced calcium dependent inactivation, preferential permeation of barium ions, and cadmium block. Consistent with reports of native Lymnaea calcium currents, the LCa(v)2a-5'rbA channel is insensitive to micromolar concentrations of omega-conotoxin GVIA and is not affected by nifedipine, thus confirming that it is not of the L-type. Interestingly, the LCa(v)2a-5'rbA channel is almost completely and irreversibly inhibited by guanosine 5'-3-O-(thio) triphosphate but not regulated by syntaxin1, suggesting that invertebrate presynaptic calcium channels are differently modulated from their vertebrate counterparts.