Characteristics of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells in vitro

An orthodromically evoked late hyperpolarizing potential (LHP) was studied using intracellular recording techniques in rat hippocampal CA1 pyramidal cells in vitro. Several tests indicated that the LHP is not blocked by GABA antagonists, but rather comprises the initial portion of the stimulation-induced burst afterhyperpolarization (AHPs) produced in the presence of these antagonists. Bath application of magnesium (Mg) or 8-bromo adenosine 3',5'-cyclic monophosphate (cAMP), or intracellular injection of ethyleneglycol-bis (beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA) blocked the late portion of the AHPs, at times when the early portion was only slightly or not at all affected. The late part of the AHPs was also associated with the voltage-dependent components of the burst, whereas the early part was not. Both the early part of the burst AHPs and the LHP in standard saline have similar time courses and dependence on membrane potential. The LHP was nullified by hyperpolarization of the membrane in extracellular potassium concentrations [( K]o) of 5.4 mM and below and could be reversed in [K]o above 5.4 mM. The apparent reversal potential for the LHP followed shifts in [K]o as predicted by the Nernst equation and is, therefore, probably a K-dependent potential. No specific antagonist of the LHP from among several K conductance blockers was found, however. An alternative hypothesis, that the LHP might be an electrogenic pump effect was not supported. Ouabain depressed the LHP; however this effect was probably nonspecific and due, in part, to a ouabain-induced increase in [K]o. Decreasing temperature in the range 37-22 degrees C prolonged but did not block the LHP. The LHP was enhanced by increases in extracellular calcium concentration and depressed by high [Mg]o or cadmium. It was associated with a small (14%) decrease in total resting input resistance. In cells depolarized to approximately 0 mV, regenerative voltage-dependent potentials were blocked; however, an LHP still occurred. The LHP was not found to be dependent on the excitatory postsynaptic potential (EPSP). With weak stimuli LHP and EPSP amplitudes were uncorrelated and the EPSP was more resistant than the LHP to block by high [Mg]o. The LHP continued to occur when the EPSP was reversed in depolarized cells. The LHP may be mediated by interneuronal circuitry within a slice. In GABA antagonists the LHP occasionally occurred spontaneously at regular intervals.(ABSTRACT TRUNCATED AT 400 WORDS)