Monoclonal antibody to the alpha 1-subunit of the dihydropyridine-binding complex inhibits calcium currents in BC3H1 myocytes.

A monoclonal antibody, mAb 1A, previously shown to recognize the dihydropyridine (DHP)-binding complex in rabbit muscle transverse tubules, inhibits voltage-sensitive calcium channel activity in a mouse muscle cell line. mAb 1A applied externally to BC3H1 muscle cells produced a concentration-dependent attenuation of the slowly-activating, DHP-sensitive, high-threshold calcium current. mAb 1A had no direct effect on either the rapidly-activating, DHP-insensitive, low-threshold calcium current or the delayed outward potassium current. However, sodium current kinetics were altered. On Western blot analysis of immunoaffinity-purified protein solubilized from BC3H1 membranes, mAb 1A recognized a Mr 210,000 polypeptide that is an analogous to the alpha 1 subunit of the DHP-binding complex from skeletal muscle. These results suggest that an extracellular segment of the alpha 1 subunit of the DHP-binding complex plays a functionally important role in voltage-gated calcium currents.