Nonspecific block of voltage‐gated potassium channels has greater effect on distal schaffer collaterals than proximal schaffer collaterals during periods of high activity

Previous studies established different responses between proximal and distal portions of Schaffer collateral axons during high-frequency and burst stimulation, with distal axons demonstrating biphasic changes in excitability (hyperexcitability followed by depression), but proximal axons showing only monophasic depression. Voltage-dependent potassium (KV) channels are important determinants of axonal excitability, and block of KV channels can promote axon hyperexcitability. We therefore hypothesized that block of KV channels should lead to biphasic response changes in proximal Schaffer collaterals, like those seen in distal Schaffer collaterals. To test this hypothesis, we made extracellular recordings of distal Schaffer collateral responses in stratum radiatum of hippocampal area CA1 and proximal Schaffer collateral responses in stratum pyramidale of area CA3 during high-frequency stimulation (HFS) at 100 Hz and burst stimulation at 200 msec intervals (5 Hz or theta frequency). We then applied a nonselective KV channel blocker, tetraethlylammonium (TEA, 10 mmol/L) or 4-aminopyridine (4-AP, 100 μmol/L), and assessed effects on Schaffer collateral responses. Surprisingly, block of KV channels had little or no effect on proximal Schaffer collateral responses during high-frequency or burst stimulation. In contrast, KV channel blockade caused more rapid depression of distal Schaffer collateral responses during both high-frequency and burst stimulation. These findings indicate that KV channels are important for maintaining distal, but not proximal, Schaffer collateral excitability during period of sustained high activity. Differential sensitivity of distal versus proximal Schaffer collaterals to KV channel block may reflect differences in channel density, diversity, or subcellular localization.