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 Ca2+-ATPase (PMCA), a ubiquitous transporter that exchanges internal Ca2+for external H+, is largely responsible for the PAT. It has also been shown that a PAT can be generated after replacing extracellular Ca2+with Ba2+. The cause of this PAT is unknown, however, because the ability of the mammalian PMCA to transport Ba2+is unclear. If the PMCA did not carry Ba2+, 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 Ba2+-containing, Ca2+-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 Ba2+-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 Ba2+is caused by the PMCA and that this transporter is responsible for the PAT whether Ca2+or Ba2+is the charge carrying divalent cation.