T-type Calcium Channels in Health and Disease.

Low Voltage-Activated (LVA) T-type calcium channels are characterized by transient current and Low Threshold Spikes (LTS) that trigger neuronal firing and oscillatory behavior. Combined with their preferential localization in dendrites and their specific "window current", T-type calcium channels are considered to be key players in signal amplification and synaptic integration. Assisted by the emerging pharmacological tools, the structural determinants of channel gating and kinetics, as well as novel physiological and pathological functions of T-type calcium channels, are being uncovered. In this review, we provide an overview of structural determinants in T-type calcium channels, their involvement in disorders and diseases, the development of novel channel modulators, as well as Structure-Activity Relationship (SAR) studies that lead to rational drug design.

The Functional and Molecular Properties, Physiological Functions, and Pathophysiological Roles of GluN2A in the Central Nervous System.

The NMDA receptor, which is heavily involved in several human brain diseases, is a heteromeric ligand-gated ion channel that interacts with multiple intracellular proteins through the C-termini of different subunits. GluN2A and GluN2B are the two primary types of GluN2 subunits in the forebrain. During the developmental period, there is a switch from GluN2B- to GluN2A-containing NMDA receptors in synapses. In the adult brain, GluN2A exists at synaptic sites more abundantly than GluN2B. GluN2A plays important roles not only in synaptic plasticity but also in mediating physiological functions, such as learning and memory. GluN2A has also been involved in many common human diseases, such as cerebral ischemia, seizure disorder, Alzheimer's disease, and systemic lupus erythematosus. The following review investigates the functional and molecular properties, physiological functions, and pathophysiological roles of the GluN2A subunit.

Emerging Roles of Hydrogen Sulfide in Inflammatory and Neoplastic Colonic Diseases.

Hydrogen sulfide (H2S) is a toxic gas that has been recognized as an important mediator of many physiological processes, such as neurodegeneration, regulation of inflammation, blood pressure, and metabolism. In the human colon, H2S is produced by both endogenous enzymes and sulfate-reducing bacteria (SRB). H2S is involved in the physiological and pathophysiological conditions of the colon, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), which makes the pharmacological modulation of H2S production and metabolism a potential chemical target for the treatment of colonic diseases. However, the exact mechanisms and pathways by which H2S-mediates normal physiological function and disease in the colon are not fully understood. Besides, the production and release of H2S are modulated by both endogenous and exogenous factors. This review will discuss the production and storage of H2S, its biological roles and the emerging importance in physiology and pathology of IBD and CRC.