T-Type Calcium Channels: A Mixed Blessing

Abstract

The role of T-type calcium channels is well established in excitable cells, where they preside over action potential generation, automaticity, and firing. They also contribute to intracellular calcium signaling, cell cycle progression, and cell fate; and, in this sense, they emerge as key regulators also in non-excitable cells. In particular, their expression may be considered a prognostic factor in cancer. Almost all cancer cells express T-type calcium channels to the point that it has been considered a pharmacological target; but, as the drugs used to reduce their expression are not completely selective, several complications develop, especially within the heart. T-type calcium channels are also involved in a specific side effect of several anticancer agents, that act on microtubule transport, increase the expression of the channel, and, thus, the excitability of sensory neurons, and make the patient more sensitive to pain. This review puts into context the relevance of T-type calcium channels in cancer and in chemotherapy side effects, considering also the cardiotoxicity induced by new classes of antineoplastic molecules.

Identification of Novel Targeting Sites of Calcineurin and CaMKII in Human CaV3.2 T-Type Calcium Channel

“…We are of the opinion that the dephosphorylation of Cav3.2, in conjunction with its phosphorylation by CaMKII or potentially other kinases, plays a crucial role in maintaining the functional homeostasis of Cav3.2. This is particularly significant considering its involvement in conditions such as chronic pain, autism, epilepsy, and primary aldosteronism [4,5].…”

“…The low-voltage-activated calcium channels, known as T-type (T for transient or tiny) channels, exhibit rapid inactivation kinetics and are capable of opening near the resting membrane potential, contributing to membrane depolarization. Vertebrates express three different T-type calcium channels: Cav3.1, Cav3.2, and Cav3.3 [3,4]. Dysfunctions in T-type calcium channels are linked to various disease conditions, including epilepsy, autism, neuromuscular disorders, and chronic pain [5].…”

Iron and atrial fibrillation: A review

“…TTCC is found in large numbers only in sinus pacemaker cells and Purkinje fibers of many species in the adult heart and is vital for maintaining pacemaker activity. 29 Furthermore, in the presence of iron overload, Kumfu et al 30 showed that the TTCC blocker nifedipine or efonidipine blocked iron uptake. Although non-selective TTCC blockers can also block LTCC, they block TTCC more effectively than LTCC.…”

“…Besides LTCC, T‐type Ca 2+ channels (TTCC) is also related to Iron metabolism. TTCC is found in large numbers only in sinus pacemaker cells and Purkinje fibers of many species in the adult heart and is vital for maintaining pacemaker activity 29 . Furthermore, in the presence of iron overload, Kumfu et al 30 .…”