Current Pharmaceutical Design - Volume 13, Issue 23, 2007

The production of new molecular entities endowed with salutary medicinal properties is a formidable challenge that involves several steps and requests rational target identification, recognition and avoidance of adverse properties of therapeutics before commitment to clinical trials, monitoring of clinical efficacy using surrogate markers and individualized approaches to disease treatment. The first to face up to is the i Read More

Ion channels play essential roles in nervous system signaling, electrolyte transport, and muscle contraction. As such, ion channels are important therapeutic targets, and the search for compounds that modulate ion channels is accelerating. In order to identify and optimize ion channel modulators, assays are needed that are reliable and provide sufficient throughput for all stages of the drug discovery process. Electroph Read More

The spontaneous activity of cardiac tissue originates in specialized pacemaker cells in the sino-atrial node that generate autonomous rhythmic electrical impulses. A number of regions in the brain are also able to generate spontaneous rhythmic activity to control and regulate important physiological functions. The generation of pacemaker potentials relies on a complex interplay between different types of currents carrie Read More

The glycine receptor (GlyR) Cl- channel belongs to the cysteine-loop family of ligand-gated ion channel receptors. It is best known for mediating inhibitory neurotransmission in motor and sensory reflex circuits of the spinal cord, although glycinergic synapses are also present in the brain stem, cerebellum and retina. Extrasynaptic GlyRs are widely distributed throughout the central nervous system and they are also found i Read More

Purinergic signaling is involved in the proper functioning of virtually all organs of the body. Although in some cases purines have a major influence on physiological functions (e.g. thrombocyte aggregation), more often they are just background modulators contributing to fine tuning of biological events. However, under pathological conditions, when a huge amount of adenosine 5'-triphosphate (ATP) can reach the extracellular sp Read More

Due to its channel-like properties, the peripheral-type benzodiazepine receptor (PBR) has been renamed the translocator protein (TSPO). In eukaryotes, the TSPO is primarily located in the outer mitochondrial membrane. In prokaryotes, it is found in the cell membrane. A broad spectrum of functions has been attributed to the TSPO, including various host defense responses, developmental processes, and mitochondrial fu Read More

Voltage-gated proton channels are highly proton selective ion channels that are present in many cells. Although their unitary conductance is 1000 times smaller than that of most ion channels, detection of single-channel currents supports their identification as channels rather than carriers. Proton channels are gated by membrane depolarization, but their absolute voltage dependence is also strongly regulated by the pH gra Read More

The intracellular hydric balance is an essential process of mammalian cells. The water movement across cell membranes is driven by osmotic and hydrostatic forces and the speed of this process is dependent on the presence of specific aquaporin water channels. Since the molecular identification of the first water channel, AQP1, by Peter Agre's group, 13 homologous members have been found in mammals with varyi Read More