The α1 Subunit EGL-19, the α2/δ Subunit UNC-36, and the β Subunit CCB-1 Underlie Voltage-dependent Calcium Currents in Caenorhabditis elegans Striated Muscle

• Published in: The Journal of biological chemistry 2011-10, Vol.286 (42), p.36180-36187
• Main Authors: Lainé, Viviane, Frøkjær-Jensen, Christian, Couchoux, Harold, Jospin, Maëlle
• Format: Article
• Language: English
• Subjects: C. elegans; Calcium Channels; Electrophysiology; Ion Channels; L-type Channels; Membrane Biology; Mutant; Plasma Membrane; Skeletal Muscle; α2/δ Subunit; β Subunit
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.256149

Voltage-gated calcium channels, which play key roles in many physiological processes, are composed of a pore-forming α1 subunit associated with up to three auxiliary subunits. In vertebrates, the role of auxiliary subunits has mostly been studied in heterologous systems, mainly because of the severe phenotypes of knock-out animals. The genetic model Caenorhabditis elegans has all main types of voltage-gated calcium channels and strong loss-of-function mutations in all pore-forming and auxiliary subunits; it is therefore a useful model to investigate the roles of auxiliary subunits in their native context. By recording calcium currents from channel and auxiliary subunit mutants, we molecularly dissected the voltage-dependent calcium currents in striated muscle of C. elegans. We show that EGL-19 is the only α1 subunit that carries calcium currents in muscle cells. We then demonstrate that the α2/δ subunit UNC-36 modulates the voltage dependence, the activation kinetics, and the conductance of calcium currents, whereas another α2/δ subunit TAG-180 has no effect. Finally, we characterize mutants of the two β subunits, CCB-1 and CCB-2. CCB-1 is necessary for viability, and voltage-dependent calcium currents are abolished in the absence of CCB-1 whereas CCB-2 does not affect currents. Altogether these results show that EGL-19, UNC-36, and CCB-1 underlie voltage-dependent calcium currents in C. elegans striated muscle. Background: The composition of voltage-gated calcium channels is important for function. Results: In C. elegans, calcium currents are altered in mutants of one main subunit (EGL-19) or the accessory subunits UNC-36 and CCB-1. Conclusion: Voltage-gated calcium channels of C. elegans striated muscles are composed of EGL-19, UNC-36, and CCB-1. Significance:C. elegans could be a new model to study the roles of accessory subunits.