Calcium antagonists have been divided into 3 different subclasses represented by nifedipine, verapamil and diltiazem. These drugs have different pharmacologic effects and are not interchangeable. Previous studies suggested that all calcium antagonists bind to a 170 kd polypeptide (now called the alpha 2 subunit of the voltage-dependent calcium channel). The apparent molecular weight of this polypeptide characteristically decreased from 170 to 140 kd upon disulfide reduction as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Recent studies demonstrated that calcium antagonists bind to a previously unrecognized 165 kd polypeptide (alpha 1 subunit) that does not change its electrophoretic mobility on disulfide reduction. Because of their similar molecular weights, the 2 polypeptides may overlap each other on polyacrylamide gels. The primary structure of both polypeptides clearly shows, however, that they are different from each other and only the alpha 1 subunit has the features expected of an ion channel.