Cholinergic-Dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons

Abstract

Cholinergic stimulation of the hippocampal formation results in excitation and/or seizure. We report here, using whole-cell patch-clamp techniques in the hippocampal slice (34 -35°C), a cholinergic-dependent slow afterdepolarization (sADP) and long-lasting plateau potential (PP). In the presence of 20 M carbachol, action potential firing evoked by weak intracellular current injection elicited an sADP that lasted several seconds. Increased spike firing evoked by stronger depolarizing stimuli resulted in long-duration PPs maintained close to Ϫ20 mV. Removal of either Na ϩ or Ca 2ϩ from the external media, intracellular Ca 2ϩ ([Ca 2ϩ ] i ) chelation with 10 mM bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetra-acetic acid, or the addition of 100 M Cd 2ϩ to the perfusate abolished both the sADP and PP. The sADP was depressed and the PP was abolished by either 10 M nimodipine or 1 M -conotoxin, whereas 1.2 M tetrodotoxin was ineffective. The involvement of a Na ϩ /Ca 2ϩ exchanger was minimal because both the sADP and PP persisted after equimolar substitution of 50 mM Li ϩ for Na ϩ in the external media or reduction of the bath temperature to 25°C. Finally, in the absence of carbachol the sADP and PP could not be evoked when K ϩ channels were suppressed, suggesting that depression of K ϩ conductances alone was not sufficient to unmask the conductance. Based on these data, we propose that a Ca 2ϩ -activated nonselective cation conductance was directly enhanced by muscarinic stimulation. The sADP, therefore, represents activation of this conductance by residual [Ca 2ϩ ] i , whereas the PP represents a novel regenerative event involving the interplay between high-voltage-activated Ca 2ϩ channels and the Ca 2ϩ -activated nonselective cation conductance. This latter mechanism may contribute significantly to ictal depolarizations observed during cholinergic-induced seizures.

A Long-Lasting Calcium-Activated Nonselective Cationic Current Is Generated by Synaptic Stimulation or Exogenous Activation of Group I Metabotropic Glutamate Receptors in CA1 Pyramidal Neurons

“…If so, other types of metabotropic receptors linked to the I P 3 production pathway (for review, see Schoepp and Conn, 1993) should activate I CAN also. In keeping with this hypothesis and in agreement with previous data (Shen and North, 1992;Colino and Halliwell, 1993;Fraser and MacVicar, 1996), we found that activation of muscarinic receptors induced a current showing similar features to those of I CAN : under perfusion with medium A, bath application of 60 -120 M carbachol (a selective agonist of muscarinic receptors linked to IP 3 production pathway) (Fisher et al, 1983(Fisher et al, , 1984Dutar and Nicoll, 1988) generated a CAN current that was smaller but otherwise comparable to I CAN induced by 1S,3R-ACPD (n ϭ 9; Fig. 6C, Table 1).…”

Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na+–Ca2+Exchange Current

“…7C) (17.4 Ϯ 2.5% of control, n ϭ 5, paired t-test, P ϭ 0.024). Because Tris or Li ϩ cannot substitute for Na ϩ in the Na ϩ -Ca 2ϩ exchanger, but can substitute for Na ϩ for the nonselective cationic channel (Fraser and MacVicar 1996;Kakehata et al 1993;Zhainazarov and Ache 1995), these findings suggested a role for the Na ϩ -Ca 2ϩ exchange current. We then tested the involvement of extracellular Ca 2ϩ .…”

“…Neither can substitute for Na ϩ in the Na ϩ -Ca 2ϩ exchanger, in contrast to the nonselective cationic channels that are permeable to both Li ϩ and Tris (Crepel et al 1994;Fraser and MacVicar 1996;Kakehata et al 1993;Partridge and Swandulla 1988;Yellen 1982;Zhainazarov and Ache 1995). Second, the current was enhanced in nominally free Ca 2ϩ , characteristic of Na ϩ -Ca 2ϩ exchange currents (Ishibashi et al 2003;Okada et al 1999;Umezu et al 2004;Wu et al 2004).…”

Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons

“…Furthermore, we examined whether channel modulations driven by other PLC-coupled receptors are also Ca 2+ dependent. We found that the activation of I-mGluRs, like muscarinic activation, induced the activation of NSC-like channels and inhibition of K + channels, and that these Many studies have shown the Ca 2+ -dependent property of NSC channel activation (Blair et al, 2009;Congar et al, 1997;Fraser and MacVicar, 1996;Gee et al, 2003;Magistretti et al, 2004;Yan et al, 2009;Zhang et al, 2011), and it has been mostly interpreted as the Ca 2+ dependence of NSC channel itself. Our data do not negate the Ca 2+ dependence of NSC channel itself, but suggest that caution must be exercised in interpreting experimental data (Blair et al, 2009).…”