Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons

“Time integration of cell assemblies at the subsecond to seconds timescale can be performed by metabotropic glutamate receptors (Nakanishi, 1994), GABAB receptors (Deisz and Prince, 1989), and slow afterhyperpolarization-associated conductances (Lancaster and Adams, 1986).”

“…DR stands for delayed rectifier, A for the A-type of transient current, AHP for the long-duration Ca-dependent AHP current (Hotson and Prince 1980; Lancaster and Adams 1986; Lancaster and Nicoll 1987; Numann et al. 1987), and C for the short-duration Ca- and voltage-dependent current (Adams et…”

“In contrast, SK channel activation underlies generation of the slow AHP after a burst of action potential”

“) are blocked by the bee-venom toxin apamin, whereas others (for example the slow K Ca current sI AHP in hippocampal pyramidal neuron”

“Studies of bullfrog sympathetic ganglion cells (Pennefather et al. 1985) and of rodent hippocampal neurons (Adams and Lancaster 1985; Lancaster and Adams 1986) has established two distinct Ca 2+- dependent K § conductances underlying the spike afterhyperpolarization.”

“The slow activation and inactivation of these currents, coupled with its high temperature sensitivity (Lancaster and Adams, 1986), may be due to the involvement of such a second messenger system.”

“Materials and Methods The experiments in this paper were performed on hippocampal slices, in vitro, prepared by standard methods (Nicoll and Alger, 198 1; Madison and Nicoll, 1986a).”

“A similar channel has also been reported in hippocampal cells (Lancaster and Adams 1986; Segal and Barker 1986).”

“When examining responses under voltage clamp, we used a hybrid clamp configuration in which the amplifier was switched into current-clamp mode in order to elicit the train of action potentials and then electronically switched back into voltage-clamp mode at the end of the train (Lancaster and Adams, 1986).”

“…by calcium influx during a burst of action potentials, that serves to modulate postsynaptic excitability of many cell types including hippocampal and cortical pyramidal neurons (Hotson and Prince, 1980; Gustafsson and Wigström, 1981; Lancaster and Adams, 1986; Storm, 1990; Schwindt et al., 1992).”

“Voltage-gated ion channel alterations What ion channel alterations might underlie the observed reduction in membrane excitability after SD? The enhanced spike frequency adaptation is presumably the result of an elevation in IAHP channel activities (Hotson and Prince, 1980; Lancaster and Adams, 1986) but could be in re…”

“(2) Although the BK-like Ca¥-dependent K¤ current in hippocampal pyramidal cells was initially described as a sustained current, IC (Lancaster & Adams, 1986), some voltage-clamp and single-channel studies also reported evidence for a fast transient, tetraethylammonium-sensitive Ca¥-dependent K¤…”

“To study the currents involved in the AHP in a more controlled and quantitative manner, we used a variant of the hybrid clamp method introduced by Lancaster and Adams (1986).”

“Even in the absence of synaptic inhibition, most neurons possess intrinsic negative feedback mechanisms that slowly bring the cell back to resting voltage levels following periods of high activity [38].”

“The small-conductance channels mediate the shift of the excitotoxic calcium mobilization into a protective, hyperpolarizing signal (Madison and Nicoll, 1984; Lancaster and Adams, 1986; Sah, 1996; Honrath et al., 2017).”

“…evidence also suggested that these channels may generate a small mAHP component (in current clamp) and a corresponding tail current (in voltage clamp) under artificial conditions (when several other K+ currents had been suppressed by 40 μm carbachol, etc.; Lancaster & Adams, 1986; Storm, 1989).”

“Like the SK channels that contribute to the ImAHP, the channels underlying the IsAHP are voltage independent and K selective, and they require Ca 2 influx for activation ( Lancaster and Adams, 1986; Sah, 1996).”

“Some of these potentials, e,g., the late after-hyperpolarization (AHP), have very long time constants of up to 100 ms and more (Lancaster and Adams 1986).”

“The postburst AHP is largely mediated by a Ca2+ -activated K+ current that clamps the cell membrane at a more hyperpolarized potential (Hotson and Prince 1980; Lancaster and Adams 1986 ) .”

“In calcium-free solution, neurons become very excitable for several reasons, including lack of calcium-activated potassium conductances, like I, involved in spike repolarization (Storm, 1987) and ZAHP, involved in spike frequency adaptation (Lancaster and Adams, 1986) and their firing thresholds are lower due to a lac…”

“More than 95% of thecells showed atypical AHPcurrent (IAHP; Lancaster and Adams, 1986) under normal conditions.”

“…and Moises, 1992) recordings from our laboratory suggest that the AHPs recorded in rat BLA neurons are similar to those found in hippocampal (Lancaster and Adams, 1986; Lancaster and Nicoll, 1987; Madison et al., 1987) and cortical (McCormick and Prince, 1986; Constanti and Sim, 1987)…”

“This conductance is responsible for a fast AHP that helps repolarize somatic action potentials in CA1 pyramidal neurons (Lancaster & Adams, 1986; Storm, 1987; Shao et al. 1999).”

“The slow afterhyperpolarization that followed the depolarizing current pulses (known to be mediated by a slow Ca 2/ -activated K / current; Lancaster and Adams 1986) was smallest in amplitude immediately after an ictal episode and increased toward the next seizure (Fig.”

“Because the AHP has a very slow time course (Lancaster and Adams, 1986; Sah and Isaacson, 1995) and responds to both”

“…I M , the slow Ca 2ϩ -activated K ϩ current I AHP , and the time-and voltage-independent leakage K ϩ curagonist muscarine (10–50 ␮M; n ϭ 5; Figures 2A and 2B) or the kainate receptor agonist kainate (100 nM; n ϭ rent) (Halliwell and Adams, 1982; Lancaster and Adams, 1986; Madison et al., 1987)”

“The efficacy of this manipulation in CA1 pyramidal cells has been established recently in experiments examining the Ca2+-dependent K+ current responsible for the slow afterhyperpolarization (Lancaster and Adams, 1986; Lancaster and Zucker, 1991, Sot.”

“The postburst AHP in hippocampal pyramidal neurons is generated largely by a Ca2'-dependent K+ current, IAHP (Hotson and Prince 1980; Lancaster and Adams 1986; Storm 1990), which in isolation is voltage and tetraethylammonium (TEA) insensitive but is reduced by cholinergic agonists (Knopfel et al.…”

“IC contributes to action potential repolarization and the fast AHP that follows single spikes (Lancaster and Adams, 1986; Lancaster and Nicoll, 1987; Storm, 1987; Sah and McLachlan, 1992).”

“SK channels underlie the slow afterhyperpolarization (sAHP; Blatz and Magleby, 1987; Sah, 1996) that limits the firing frequency during a train of action potentials (Madison and Nicoll, 1984; Lancaster and Adams, 1986; Hille, 1992; Sah, 1996).”

“…a longlasting (> 1 s) after-hyperpolarization current following a depolarizing prepulse (Shah & Haylett, 2000), characteristic of pyramidal cells (Lancaster & Adams, 1986; Storm, 1990), but not of interneurons (Savic et al. 2001); (3) the presence of mRNA for the vesicular glutamate transporter…”

“To evoke and study in a quantitative manner the currents underlying single-spike afterhyperpolarization, a protocol based on principles outlined by Lancaster and Adams (1986) was applied.”

“To compare the Ca(2) -activated K currents (AHP currents; Pennefather et al., 1985; Lancaster and Adams, 1986; Storm, 1990; Stocker et al., 1999) in the three cell populations, each cell was voltage-clamped at a holding potential of 50 or 55 mV.”

“In contrast, the slow AHP recorded from hippocampal pyramidal neurons follows a slower time course, decaying over several seconds, and is insensitive to apamin (Lancaster and Adams, 1986; Storm, 1987).”

“…c ϭ Ϫ30mV , 2 d ϭ d ϱ ͓͑Ca 2ϩ ͔ i ͒ ␴ c ϭ 7mV , c ϱ ͑V͒ ϭ ͕1 ϩ exp͓ Ϫ ͑V Ϫ ␪ c ͒ / ␴ c ͔͖ Ϫ1 a c ϭ 6 d ϱ ͓͑Ca 2ϩ ͔ i ) ϭ ( 1ϩa c / ͓Ca 2ϩ ͔ i ͒ Ϫ1 I sAHP , q dq / dt ϭ ͓q ϱ ͓͑Ca 2ϩ ͔ i ͒ Ϫ q͔ / ␶ q ␶ q ϭ 450 a q ϭ 2 2 q ϱ ͓͑Ca 2ϩ ͔ i ͒ ϭ ͑1 ϩ a q 4 / ͓Ca 2ϩ ͔ i 4 ͒ Ϫ1 References and comments : 1 )…”

“…Lazdunski, 1984); Apl~~~ia (Deitmer and Eckert, 1985), bullfrog sympathetic neurons (Goh and Pennefather, 1987), GH, pituitary cells (Ritchie, 1987), rat sympathetic neurons (Kawai and Watanabe, 1986; Smart, 1987), and rat hippocampal neurons (Brown and Griffith, 1983; Lancaster and Adams, 1986).”

“In hippocampal pyramidal neurons, the slow AHP is insensitive to apamin, exhibits very slow kinetics, and is modulated by neurotransmitter-induced second messengers such as protein kinase A (PKA) [ 17 , 20,23].”

“large-conductance calcium-activated potassium (BK) channels (Lancaster and Adams, 1986; Lancaster and Nicoll, 1987); mAHPs are generated by SK currents (Schwindt et al.”

“In contrast, apamin-insensitive AHPs such as are seen in hippocampal pyramidal neurons, have a rising phase and then decay over several seconds.(2,4) This distinction is also seen in cells”

“Although the membrane voltage was not precisely controlled during the depolarizing step because of the gain and space-clamp limitations, voltage control of the AHP tail current was well maintained (Lancaster and Adams, 1986; Constanti and Sim, 1987; Sah and McLachlan, 1991; Zhang et al., 1995).”

“…pyramidal neurons, repetitive firing activates the slow afterhyperpolarization current (sIAHP, see Section 1.2 for adescription of the AHP, Hotson & Prince, 1980; Lancaster & Adams, 1986; Storm, 1989), which hyperpolarizes the somatic and proximal dendritic membrane potential (Sah & Bekkers, 1996).”

“The methylsulfate anion was used because it has been shown to preserve IsAHP in a form similar to that observed with sharp electrode recordings (Lancaster and Adams, 1986).”

“voltage-activated potassium currents in hippocampal pyramidal neurons: IA, ID, and IK (Gustafsson et al., 1982; Segal and Barker, 1984; Zbicz and Weight, 1985; Lancaster and Adams, 1986; Numann et al., 1987; Sah et al., 1988; Storm, 1988; Lancaster et al., 1991; Klee et al., 1995; Bossu et al., 1996).”

“The postburst AHP is primarily comprised of an outward, calcium-activated K(1) current that modulates postsynaptic excitability of many cell types, including hippocampal and cortical pyramidal neurons (Hotson and Prince, 1980; Gustafsson and Wigström, 1981; Lancaster and Adams, 1986; Schwindt et al., 1992; Storm, 1990…”

“Consistent with the proposed role of BK channels in many cell types (Pennefather et al., 1985; Lancaster and Adams, 1986; Lang and Ritchie, 1987, 1990), both BK, and BK, currents contribute to action potential repolarization in chromaffin cells.”

“In particular, in neurones, currents originating from SK channels are thought to be responsible for the slow afterhyperpolarization (sAHP) following an action potential [10, 18 , 20, 25, 26, 28, 34].”