Calcium- and barium-dependent extracellular alkaline shifts evoked by electrical activity in rat hippocampal slices.
Synaptic activation of central neurons has been associated with rapid extracellular alkalinization. In this report, we directly activated CA1 pyramidal cells by antidromic invasion, or by field stimulation. Antidromic activation produced no pH change, despite a robust population spike in five of 11 slices. In six slices, antidromic stimulation at 10 Hz evoked a small alkalinization in stratum pyramidale (0.04 +/- 0.01 unit pH) which grew to 0.10-0.20 unit pH at 50-100 Hz, and was blocked in 0 Ca2+ media. Simultaneous pH recordings revealed no alkalinizations in stratum radiatum, despite robust alkaline shifts in stratum pyramidale. When synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, DL-2-amino-5-phosphonovalerate and picrotoxin, the Schaffer collateral-induced alkaline shift in stratum radiatum was abolished. With adequate stimulus strength and orientation, however, alkaline shifts in stratum radiatum could still be elicited, presumably by direct activation of the CA1 population. The non-synaptic alkaline shifts ranged from 0.10-0.20 unit pH, were amplified by benzolamide, and blocked by tetrodotoxin, 0 Ca2+ saline, and 300-400 microM Cd2+. Although directly activated alkaline shifts were never observed in 0 Ca2+ saline, large stimulus evoked responses could be elicited upon addition of 5-10 mM Ba2+. The Ba(2+)-dependent responses were also amplified by benzolamide and blocked by tetrodotoxin, Cd2+ or high Mg2+. These data demonstrate that stratum pyramidale can undergo an extracellular alkaline shift independent of stratum radiatum. The ionic dependence and pharmacologic sensitivity of the alkaline shifts suggest that voltage-gated Ca2+ channels are instrumental in triggering the alkalinizing mechanism. However, the ability of Ba2+ to support the alkaline shifts indicates that Ca2+ entry is not an absolute requirement. Implications for the mechanism of these pH changes are discussed.
Grichtchenko
I I
II
Department of Physiology and Neuroscience, New York University Medical Center, NY 10016, USA.
Chesler
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001464:Barium; D002118:Calcium; D015220:Calcium Channels; D010852:Picrotoxin; D013779:Tetrodotoxin