ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

Effect of catecholamines on rat medullary thick ascending limb chloride transport: interaction with angiotensin II

Previous studies have shown that in proximal and distal tubule nephron segments, peritubular ANG II stimulates sodium chloride transport. However, ANG II inhibits chloride transport in the medullary thick ascending limb (mTAL). Because ANG II and catecholamines are both stimulated by a decrease in extracellular fluid volume, the purpose of this study was to examine whether there was an interaction between ANG II and catecholamines to mitigate the inhibition in chloride transport by ANG II. In isolated perfused rat mTAL, 10−8 M bath ANG II inhibited transport (from a basal transport rate of 165.6 ± 58.8 to 58.8 ± 29.4 pmol·mm−1·min−1; P < 0.01). Bath norepinephrine stimulated chloride transport (from a basal transport rate of 298.1 ± 31.7 to 425.2 ± 45.8 pmol·mm−1·min−1; P < 0.05) and completely prevented the inhibition in chloride transport by ANG II. The stimulation of chloride transport by norepinephrine was mediated entirely by its β-adrenergic effect; however, both the β- and α-adrenergic agonists isoproterenol and phenylephrine prevent the ANG II-mediated inhibition in chloride transport. In the presence of 10−5 M propranolol, the effect of norepinephrine to prevent the inhibition of chloride transport by ANG II was still present. These data are consistent with an interaction of both α- and β-catecholamines and ANG II on net chloride transport in the mTAL