Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes.
1. The electrophysiological and pharmacological properties of slow afterpotentials in large layer V neurons from cat sensorimotor cortex were studied in an in vitro slice preparation using intracellular recording and single-microelectrode voltage clamp. These properties were used to assess the role of afterpotential mechanisms in prolonged excitability changes. 2. The mean duration of a slow afterhyperpolarization (sAHP) was 13.5 s following 100 spikes evoked at 100 Hz. Its time course was best described by two exponential components, which decayed with time constants of several hundred milliseconds (the early sAHP) and several seconds (the late sAHP). The amplitude of both the early and late components were sensitive to membrane potential and raised extracellular K+ concentration [( K+]o). 3. The early sAHP was reduced when divalent cations were substituted for Ca2+, whereas the late sAHP was unaffected. We conclude that a Ca2+-mediated K+ conductance is responsible for much of the early sAHP. In the presence of tetrodotoxin (TTX), 1-s voltage-clamp steps were used to evoke slow AHPs or outward ionic currents. These AHPs and currents were abolished in Ca2+-free perfusate, but they had a maximum duration of only a few seconds. Thus the slowest outward currents we could observe during voltage clamp in TTX were responsible only for the early sAHP. 4. The possible role of an electrogenic Na+-K+ pump in the late sAHP was examined by applying ouabain to the slice. Ouabain did not reduce selectively the late sAHP, and its effect was best explained by a decrease in intracellular K+ concentration and an increase in [K+]o. 5. Muscarinic and beta-adrenergic agonists reduced or abolished the entire (early and late) sAHP. Neither type of agonist affected the Ca2+-dependent, apamin-sensitive medium-duration afterhyperpolarization (35). We conclude that both the Ca2+-mediated K+ conductance underlying the early sAHP and the Ca2+-independent mechanisms underlying the late sAHP are sensitive to at least two classes of transmitter agonists. 6. We focused on the muscarinic effects. When concentrations greater than 5 microM were employed, the entire (early and late) sAHP was replaced by a slow afterdepolarization (sADP). Muscarine reduced the sAHP directly by reducing the underlying outward ionic currents and indirectly by causing the sADP. The sADP was Ca2+-mediated, since it was abolished by Ca2+-free perfusate but not by TTX. 7. The ionic currents underlying the sAHP and the sADP influenced excitability for seconds following evoked repetitive firing.(ABSTRACT TRUNCATED AT 400 WORDS)
Schwindt
P C
PC
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
Spain
W J
WJ
Foehring
R C
RC
Chubb
M C
MC
Crill
W E
WE
D000818:Animals; D001696:Biomechanical Phenomena; D002415:Cats; D004553:Electric Conductivity; D066298:In Vitro Techniques; D009044:Motor Cortex / Q000502:physiology*; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000502:physiology*; D013997:Time Factors
D009116:Muscarine; D009638:Norepinephrine