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Differential control of three after‐hyperpolarizations in rat hippocampal neurones by intracellular calcium buffering
Author(s) -
Velumian Alexander A.,
Carlen Peter L.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0201z.x
Subject(s) - bapta , chemistry , biophysics , hyperpolarization (physics) , intracellular , hippocampal formation , calcium , neuroscience , depolarization , calcium in biology , endocrinology , biochemistry , biology , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
1 The whole‐cell recording technique, combined with internal perfusion, was used to study the effects of intracellular Ca 2+ buffering on fast, medium and slow after‐hyperpolarizations (fAHP, mAHP and sAHP) in hippocampal CA1 pyramidal neurones in rat brain slices at room temperature. 2 The action potentials and the fAHP were unaffected by 100 μM to 3 mM concentrations of the internally applied fast Ca 2+ chelator BAPTA. At higher (10‐15 mM) concentrations, BAPTA inhibited the fAHP and prolonged the decay of the action potential, suggesting that the corresponding large‐conductance Ca 2+ ‐activated K + channels are located close to the sites of Ca 2+ entry during an action potential. Addition of Ca 2+ to the BAPTA‐containing solution (at a ratio of 4·5 [Ca 2+ ] : 10 [BAPTA]) to maintain the control level of [Ca 2+ ] i did not prevent the effects of high concentrations of BAPTA. 3 The mAHP, activated by a train of action potentials, was inhibited by internally applied BAPTA within the range of concentrations used (100 μM to 15 mM), and this effect could not be reversed or prevented by addition of Ca 2+ to the BAPTA‐containing solution. The inhibition of the mAHP by BAPTA could also be observed after blockade of the hyperpolarization‐activated I Q type mixed Na + ‐K + current (also known as I h ) component of the mAHP by bath‐applied 3‐5 mM Cs + , suggesting that the inhibition of the mAHP by BAPTA is due to inhibition of the depolarization‐activated I M (muscarinic) type K + current. 4 The sAHP, activated by a train of action potentials, was potentiated by 100‐300 μM internally applied BAPTA, both with and without added Ca 2+ . At 1‐2 mM or higher concentrations, the potentiation of the sAHP by BAPTA without added Ca 2+ was transient and was followed by a fast decrease. With added Ca 2+ , however, BAPTA caused a persistent potentiation of the sAHP with more than a 10‐fold increase in duration for periods exceeding 1 h even at concentrations of the buffer as high as 10‐15 mM. Earlier reports showing a blockade of the sAHP by BAPTA, based on experiments without added Ca 2+ , were apparently due to a sharp reduction in intracellular free [Ca 2+ ] and to a high intracellular concentration of the free buffer. 5 Internally applied BAPTA caused a prolongation of the spike discharge during an 800 ms‐long depolarizing current step. At 100‐300 μM BAPTA, but not at 1‐2 mM or higher concentrations, this effect could be reversed by addition of Ca 2+ . The effects of BAPTA on the spike discharge occurred in parallel with the changes in the sAHP time course, which was more prolonged at higher concentrations of the buffer. 6 The concentration‐dependent differential control of the three types of AHP in hippocampal neurones by BAPTA is related to modulation of intracellular Ca 2+ diffusion by a fast acting mobile Ca 2+ buffer.