MOLECULAR-PROPERTIES OF VOLTAGE-DEPENDENT CA2+ CHANNELS IN EXCITABLE TISSUES

Voltage-gated Ca2+ channels in the plasma membrane of electrically excitable cells mediate the entry of Ca2+ ions into the cell upon membrane depolarization. Different channel types have been described that differ with respect to their biophysical, pharmacological and biochemical properties. Drugs inhibiting so-called L-type Ca2+ channels in cardiac and smooth muscle ('Ca2+ antagonists') are clinically used to treat cardiovascular disorders like angina pectoris and hypertension. Various subunits participating in the formation of functional Ca2+-channel complexes have been cloned and sequenced from several tissues. We give a brief overview of the different Ca2+-channel types, their known physiological function and their modulation by first and second messengers, drugs and toxins. The molecular properties of the different channel subunits and their role for channel function and modulation will be discussed. We will especially focus on the structure of the ion pore-forming subunits, the alpha1-subunits. Recent work allowed to identify regions within their primary structure responsible for various functional properties including divalent cation selectivity and L-type-channel drug binding.