Cloning and expression of a jellyfish calcium channel beta subunit reveal functional conservation of the alpha(1)-beta interaction

In high voltage-activated calcium channels, the binding between the pore-fo rming alpha(1) subunit and the modulatory beta subunit is mediated by inter action domains in each molecule that are highly conserved among most known subunits. However, the interaction domain within CyCa alpha(1), an alpha(1) subunit cloned from the jellyfish Cyanea capillata, matches the canonical sequence of the alpha(1) interaction domain at only four of nine sites. We have now cloned a cDNA from Cyanea neuromuscular tissue that encodes a Ca2 channel beta subunit. The subunit, named CyCa beta, shares 47-54% identity with vertebrate beta subunit isoforms, but is most highly conserved within its interaction domain. Coexpression of CyCa beta with CyCa alpha(1) in Xe nopus oocytes increases the amplitude of the CyCa alpha(1) current and shif ts its activation to more hyperpolarized potentials. These responses are mi micked by coexpression of the rat beta(2a) subunit, demonstrating that the alpha(1)-beta interaction is functionally conserved between cnidarians and mammals. CyCa beta also markedly accelerates the rate of recovery of CyCa a lpha(1) from inactivation, an action that is modestly duplicated by beta(2a ) and may represent an additional mechanism by which beta subunit isoforms differentially modulate alpha(1) subunits. These findings establish that li mited conservation within the al interaction domain is sufficient to allow full modulation by a beta subunit, as well as altered regulation by differe nt beta isoforms.