AbstractT‐type channels are unique among the voltage‐gated calcium channels in their fast kinetics and low voltages of activation and inactivation, the latter two features allowing them to operate at voltages near the resting membrane potential of most neurons. T‐type channels can therefore be recruited by subthreshold depolarizations, and hyperpolarizations that remove inactivation. As such, T‐type channels can significantly influence how and when cells reach action potential threshold, and thus are critical regulators of excitability. T‐type channels are also significantly conserved within the animal kingdom, present even in animals lacking muscles and nerves, suggesting that they evolved before or very early on during the emergence of neuronal and neuromuscular synapses. Physiologically, T‐type channels are involved in multiple processes, and their contributions range from purely electrogenic roles to the activation of calcium‐sensitive ion channels, signaling pathways, and other macromolecular complexes. Unfortunately, it has been difficult to prove sufficiency and necessity of T‐type channels in many of these processes, in part due to inconsistencies in their suspected contributions. Furthermore, gene knockout studies have failed to show that T‐type channels are essential for development or survival, as knockout animals exhibit only weak phenotypes. T‐type channels roles are likely dependent on cellular context, and the three mammalian isotypes are expected to be somewhat redundant in their functionality, but have evolved from the single ancestral precursor gene in invertebrates to carry out unique functions, as evidenced by their divergent biophysical properties and protein–protein interaction motifs present within cytoplasmic regions.WIREs Membr Transp Signal2012, 1:467–491. doi: 10.1002/wmts.41For further resources related to this article, please visit theWIREs website.
