Non-synaptic modulation of repetitive firing by adenosine is antagonized by 4-aminopyridine in a rat hippocampal slice.

In rat hippocampal slices which were superfused with low calcium (0.2 mM) medium, stimulation of the alvear fibers elicited an extracellularly recorded antidromic population spike in CA1 pyramidal neurons which was followed by 2-4 afterpotentials. Adenosine (20-40 microM) and the A1-adenosine agonist 1-phenylisopropyladenosine (L-PIA) blocked these afterpotentials without affecting the first spike. Addition of up to 5 mM tetraethylammonium to the superfused medium did not interfere with this adenosine action. But the addition of only 50 microM 4-aminopyridine (4-AP) antagonized almost completely the adenosine- or L-PIA-induced depression of antidromically evoked repetitive firing. It is concluded that functioning of 4-AP-sensitive potassium channels is a prerequisite for this 'antiepileptic' adenosine action. Since a similar pharmacological characteristic has been described for the A-current, it is likely that adenosine acts by turning on this particular potassium current.