Abstract
In hippocampal pyramidal cells, a single action potential (AP) or
a burst of APs is followed by a medium afterhyperpolarization (mAHP,
lasting approximately 0.1 s). The currents underlying the mAHP are
considered to regulate excitability and cause early spike frequency
adaptation, thus dampening the response to sustained excitatory input
relative to responses to abrupt excitation. The mAHP was originally
suggested to be primarily caused by M-channels (at depolarized potentials)
and h-channels (at more negative potentials), but not SK channels.
In recent reports, however, the mAHP was suggested to be generated
mainly by SK channels or only by h-channels. We have now re-examined
the mechanisms underlying the mAHP and early spike frequency adaptation
in CA1 pyramidal cells by using sharp electrode and whole-cell recording
in rat hippocampal slices. The specific M-channel blocker XE991 (10
microm) suppressed the mAHP following 1-5 APs evoked by current injection
at -60 mV. XE991 also enhanced the excitability of the cell, i.e.
increased the number of APs evoked by a constant depolarizing current
pulse, reduced their rate of adaptation, enhanced the after depolarization
and promoted bursting. Conversely, the M-channel opener retigabine
reduced excitability. The h-channel blocker ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium
chloride; 10 microm) fully suppressed the mAHP at -80 mV, but had
little effect at -60 mV, whereas XE991 did not measurably affect
the mAHP at -80 mV. Likewise, ZD7288 had little or no effect on excitability
or adaptation during current pulses injected from -60 mV, but changed
the initial discharge during depolarizing pulses injected from -80
mV. In contrast to previous reports, we found that blockade of Ca$^2+$-activated
K$^+$ channels of the SK/KCa type by apamin (100-400 nm) failed
to affect the mAHP or adaptation. A computational model of a CA1
pyramidal cell predicted that M- and h-channels will generate mAHPs
in a voltage-dependent manner, as indicated by the experiments. We
conclude that M- and h-channels generate the somatic mAHP in hippocampal
pyramidal cells, with little or no net contribution from SK channels.
- 15890705
- action
- adaptation,
- animals,
- biological
- cal,
- calcium-activated
- calcium-activated,
- cells,
- channel
- channel,
- channels,
- clocks,
- comparative
- feedback,
- gating,
- gov't,
- hippocampus,
- ion
- kcnq
- kcnq1
- long-term
- male,
- non-u.s.
- ntials,
- physiologi,
- potassium
- pote,
- potentiation,
- pyramidal
- rats,
- research
- small-conductance
- study,
- support,
- voltage-gated,
- wistar,
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