A calcium-dependent slow afterdepolarization recorded in rat dorsolateral septal nucleus neurons in vitro

1. Conventional intracellular and single-electrode voltage-clamp recordings were obtained from rat brain slices containing dorsolateral septal nucleus (DLSN) neurons in vitro. 2. We observed a slow afterdepolarizing potential (slow-ADP) that lasted up to several seconds (half-decay time was in the range of 0.7-1.4 s) in almost 15% of DLSN neurons; these same neurons could exhibit burst firing activity. The amplitude of this slow-ADP was not affected by hyperpolarization of the membrane potential. 3. The slow-ADP was associated with an increased membrane conductance. Hybrid voltage clamping of the slow-ADP revealed a transient slow inward current (slow-ADC). The current-voltage relationship of the slow-ADC was linear between -40 and -100 mV and generated an extrapolated reversal potential of -30 mV. 4. We investigated the ionic mechanism of the slow-ADP in the rat DLSN. Slow-ADPs were not blocked by 1 microM tetrodotoxin (TTX) but were markedly depressed by 200 microM Cd2+, Ca2(+)-free, low-Na+ solutions, and the intracellular injection of ethylene glycol-bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Neither diltiazam (10 microM), an L-type Ca2+ channel blocker nor omega-conatoxin (0.2-2.5 microM), an N-type Ca2+ channel blocker affected the slow-ADP. Similarly, the slow-ADP was not affected in a low-Cl- solution. On the other hand, the slow-ADP was enhanced in a K(+)-free solution. In addition, the slow-ADP was not affected by 1 mM kynurenic acid, a broad-spectrum excitatory amino acid antagonist. 5. We conclude that the slow-ADP in the rat DLSN is mediated by a novel Ca2(+)-dependent, Na(+)-dependent, and nonsynaptic inward current that may be similar to the Ca2(+)-activated nonspecific cation channel currents (i.e., CAN-currents) described in various tissues. This current appears to underlie some forms of spontaneous bursting activity recorded from rat DLSN neurons. It may also be responsible for some types of bursting activity recorded in other CNS neurons.