Differential time-course of slow afterhyperpolarizations and associated Ca2+ transients in rat CA1 pyramidal neurons: further dissociation by Ca2+ buffer

Neuroscience. 1999;88(3):719-26. doi: 10.1016/s0306-4522(98)00203-6.


Hippocampal neurons exhibit a slow afterhyperpolarization following membrane depolarization; this is thought to reflect an underlying Ca2+-dependent K+ current. This current is potentiated by intermediate concentrations (0.1-1.0 mM) of exogenous Ca2+ buffer [Schwindt P. C. et al. (1992) Neuroscience 47, 571-578; Zhang L. et al. (1995) J. Neurophysiol. 74, 2225-2241]. The relationship between the slow afterhyperpolarization and associated Ca2+ transients was investigated in the presence and absence of added exogenous Ca2+ buffer. Slow afterhyperpolarizations and underlying K+ currents were measured using whole-cell patch-clamp recordings from hippocampal CA1 neurons in acute rat brain slices. Inclusion of fluorescent Ca2+ indicators in the patch pipette solution allowed simultaneous measurement of the evoked subcellular Ca2+ transients using a confocal microscope. The peak Ca2+ signal exhibited an incremental increase with each action potential. This increase eventually reached a plateau with increasing numbers of action potentials, suggesting dye saturation with peak Ca2+ concentrations. As the K(D) for Ca2+ of the indicator dyes used was between 200 and 300 nM, it is predicted that saturation will occur when the peak Ca2+ signal exceeds 1 microM. This occurred with fewer action potentials in dendritic vs somatic compartments. Neither compartment exhibited averaged Ca2+ transients matching the slow afterhyperpolarization time-course, dendritic Ca2+ transients being most divergent. Intracellular accumulation of exogenous Ca2+ buffer, either by inclusion in the patch pipette or by incubation of the brain slice with its membrane-permeable form, caused a prolongation of the slow afterhyperpolarization but not of the somatic Ca2+ transient. The initial rate of decline of the dendritic Ca2+ transient was diminished, but remained faster than that of the slow afterhyperpolarization. We conclude that neither dendritic nor somatic Ca2+ signals match the slow afterhyperpolarization time-course, with this dissociation being further magnified by addition of exogenous Ca2+ buffer. The implications of this result are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Brain / physiology*
  • Buffers
  • Calcium / metabolism*
  • Chelating Agents / pharmacology
  • Coloring Agents
  • Dendrites / drug effects
  • Dendrites / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Time Factors


  • Buffers
  • Chelating Agents
  • Coloring Agents
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium