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Potassium currents in acutely isolated human hippocampal dentate granule cells.

1. Properties of voltage‐ and Ca(2+)‐dependent K+ currents were investigated in thirty‐four dentate granule cells acutely isolated from the resected hippocampus of eleven patients with therapy‐refractory temporal lobe epilepsy (TLE). 2. When intracellular Ca2+ was strongly buffered with 11.5 mM EGTA‐1 mM Ca2+ in the recording pipette, K+ currents (IK) with a slow activation and biexponential time‐dependent decay could be elicited, which showed a threshold for activation around ‐30 mV. 3. A contribution of Ca(2+)‐dependent K+ currents became apparent with intracellular solution containing 1 mM BAPTA‐0.1 mM Ca2+. Superfusion of low‐Ca2+ extracellular solution blocked 43% of outward currents in this recording configuration. Outward current components could also be blocked by substituting 5 mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%). 4. The Ca(2+)‐dependent K+ currents could be pharmacologically subdivided into two components. One component was sensitive to 500 microM tetraethylammmonium (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM CTX and 500 microM TEA were not additive, suggesting that both agents block the same conductance. A second, smaller outward current component was blocked by 50 nM apamin (13%). 5. A transient A‐type K+ current could be observed in six neurones and showed a fast monoexponential time‐dependent inactivation with a steady‐state voltage dependence that was distinct from that of IK. The A‐type current was blocked by 4‐aminopyridine (4‐AP) but not by TEA or low‐Ca2+ solution. 6. We conclude that outward currents in human hippocampal dentate granule cells can be separated into at least four types by their kinetic and pharmacological properties. These include at least one voltage‐dependent current similar to those observed in mammalian hippocampal neurones, and two Ca(2+)‐dependent K+ currents that most probably correspond to SK‐ and BK‐type currents. A classical A‐type current could be detected in some patients with Ammon's horn sclerosis (AHS) but not in patients with lesion‐associated TLE.