title: Barium plateau potentials of CA1 pyramidal neurons elicit all-or-none extracellular alkaline shifts via the plasma membrane calcium ATPase.
abstract: In many brain regions, synchronous neural activity causes a rapid rise in extracellular pH. In the CA1 region of hippocampus, this population alkaline transient (PAT) enhances responses from postsynaptic, pH-sensitive N-methyl-d-aspartate (NMDA) receptors. Recently, we showed that the plasma membrane Ca(2+)-ATPase (PMCA), a ubiquitous transporter that exchanges internal Ca(2+) for external H(+), is largely responsible for the PAT. It has also been shown that a PAT can be generated after replacing extracellular Ca(2+) with Ba(2+). The cause of this PAT is unknown, however, because the ability of the mammalian PMCA to transport Ba(2+) is unclear. If the PMCA did not carry Ba(2+), a different alkalinizing source would have to be postulated. Here, we address this issue in mouse hippocampal slices, using concentric (high-speed, low-noise) pH microelectrodes. In Ba(2+)-containing, Ca(2+)-free artificial cerebrospinal fluid, a single antidromic shock to the alveus elicited a large (0.1-0.2 unit pH), "all-or-none" PAT in the CA1 cell body region. In whole cell current clamp of single CA1 pyramidal neurons, the same stimulus evoked a prolonged plateau potential that was similarly all-or-none. Using this plateau as the voltage command in other cells, we recorded Ba(2+)-dependent surface alkaline transients (SATs). The SATs were suppressed by adding 5 mM extracellular HEPES and abolished when carboxyeosin (a PMCA inhibitor) was in the patch pipette solution. These results suggest that the PAT evoked in the presence of Ba(2+) is caused by the PMCA and that this transporter is responsible for the PAT whether Ca(2+) or Ba(2+) is the charge carrying divalent cation.
authors.affiliation: Dept. of Physiology and Neuroscience, NYU Langone Medical Center, 550 First Ave., New York, NY 10016, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Makani
authors.forename: Mitchell
authors.initials: M
authors.lastname: Chesler
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D001464:Barium; D053499:Plasma Membrane Calcium-Transporting ATPases