Until recently the mechanisms that allowed the chief cells of the parathyroid glands to secrete parathyroid hormone (PTH) at a rate that is responsive to the extracellular calcium ion concentration (Ca o ) remained obscure (Brown 1991). The cloning of an extracellular calcium ion-sensing receptor (CaR) from bovine parathyroid tissue has defined an important step in the regulatory pathway of thi...

The effects of changes in the extracellular pH (pH(o)) on low-voltage- (LVA) and high-voltage- (HVA) activated calcium currents of acutely isolated relay neurons of the ventrobasal thalamic complex (VB) were examined using the whole cell patch-clamp technique. Modest extracellular alkalinization (pH 7.3 to 7.7) reversibly enlarged LVA calcium currents by 18.6 +/- 3.2% (mean +/- SE, n = 6), wher...

We found that a negative calcium-responsive element (nCaRE) originally reported in the human parathyroid hormone gene is conserved among several genes. The results of the present study show that expression of one of the genes, the rat atrial natriuretic polypeptide gene, was negatively regulated in the heart by extracellular calcium by using an in vivo infusion system. Moreover, transfection of...

The capacity to regulate their internal ionic composition is a fundamental property of free-living terrestrial organisms (Stewari and Broadus, 1987). This is accomplished by adjusting the movement of ions or water (or both) between cells and various extracellular compartments, including those communicating with the external environment. Of the complement of inorganic ions in such organisms, Ca2...

We have studied block of L-type calcium channels by intracellular and extracellular application of the ionized dihydropyridine derivatives amlodipine and SDZ 207-180. We find that extracellular application of either drug causes voltage-dependent block of calcium channels. However, neither drug is effective when applied intracellularly. The insensitivity of calcium channels to intracellular drug...

Calcium is a crucial signal molecule in the cardiovascular system. Calcium (Ca 2+ ) acts as a second messenger via changes in intracellular Ca 2+ levels through the actions of calcium channels and pumps. However, it is now well known that calcium may also be an extracellular first messenger through a G-protein-coupled receptor that senses extracellular Ca 2+ concentration, the calcium-sensing r...

Though both clinicians and scientists have long recognized the influence of extracellular calcium on the function of muscle and nervous tissue, recent insights reveal that the mechanisms allowing changes in extracellular calcium to alter cellular excitability have been incompletely understood. For many years the effects of calcium on neuronal signaling were explained only in terms of calcium en...

Platelet release by megakaryocytes is regulated by a concert of environmental and autocrine factors. We previously showed that constitutively released adenosine diphosphate by human megakaryocytes leads to platelet production. Here we show that adenosine diphosphate elicits, in human megakaryocytes, an increase in cytosolic calcium concentration, followed by a plateau, which is lowered in the a...

One fifth of the mammalian brain is comprised of extracellular space (ECS). The extracellular space is not empty, but instead comprises a complex network of proteins and a variety of molecular species. One extracellular species, calcium, holds a prominent position as one of the most important messengers known in the brain. However, calcium exists in low concentrations in the ECS, and its diffus...

Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca(2+)](o)) regulates Ca(2+) entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fu...