Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro

P. C. Schwindt, W. J. Spain, R. C. Foehring, C. E. Stafstrom, M. C. Chubb, W. E. Crill

Research output: Contribution to journalArticle

Abstract

1. Potassium conductances were studied in larger layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp and indirectly by evoking single or multiple spikes and recording the spike repolarization and subsequent afterhyperpolarizations (AHPs). 2. A fast-decaying afterhyperpolarization (fAHP) and a subsequent medium-duration afterhyperpolarization (mAHP) followed a single spike. The amplitude and duration of the mAHP increased when multiple spikes were evoked at a fast rate (e.g., 100 Hz), and a slower afterhyperpolarization (sAHP) appeared only after sustained repetitive firing. 3. All AHPs were reduced by membrane potential hyperpolarization and raised extracellular K+ concentration, suggesting they were caused by an increased K+ conductance. Only the mAHP and sAHP reversed at the estimated value of potassium equilibrium potential (-100 mV), whereas the mean reversal potential of the fAHP was nearly identical to the mean value of resting potential (-71 mV). 4. Mechanisms underlying spike repolarization, the fAHP, and the mAHP were investigated. Two rapidly activating outward currents, a fast-inactivating current and a slowly inactivating delayed rectifier, were detected by voltage clamp. Both currents were reduced rapidly by tetraethylammonium (TEA). The fast transient current was reduced slowly after divalent cations were substituted for Ca2+ (through a mechanism unrelated to blockade of Ca2+ channels), whereas the delayed rectifier was unaffected. 5. Spike duration was increased and the fAHP was abolished only by blocking agents that reduced the fast outward currents. Effects of extracellular and intracellular TEA were similar. Effects of TEA and Ca2+-free perfusate were additive and resembled the effects of intracellular Cs+. The addition of apamin, d-tubocurare, or Cd2+ was ineffective. We conclude that the two fast outward currents reflect pharmacologically and kinetically separate K+ conductances that are primarily responsible for spike repolarization and the fAHP. 6. Voltage-clamp studies revealed two additional outward currents, which were persistent and Ca2+-mediated. Each current activated and deactivated slowly, but the kinetics of one component were ~ 10 times slower than the other. The decay of these currents gave rise to AHPs resembling the mAHP and the early sAHP. 7. Neither the mAHP nor the sAHP was reduced by TEA. The mAHP was reduced when divalent cations were substituted for Ca2+ or when Cd2+, apamin, or d-tubocurare were added. The sAHP was not affected by the latter two agents. We conclude that the mAHP reflects a relatively slow, persistent, apamin-sensitive, Ca2+-mediated K+ conductance. Pharmacological properties of the sAHP are described in the following paper. 8. Pharmacological reduction of the fast K+ conductances led to burst firing in response to injected current pulses. Apparently, the bursting results from inadequate spike repolarization in the face of powerful inward ionic currents activated during the action potential and by subthreshold depolarization. We conclude that the fast K+ currents normally prevent this burst firing. 9. Selective abolition of the mAHP resulted in a steeper relation between firing rate and injected current (the f-I curve), but the slow adaptation of firing rate during prolonged stimulation was preserved. We conclude that the persistent K+ conductance underlying the mAHP influences significantly the firing rate occurring at any instant during prolonged stimulation, but not the time course of slow adaptation. Ca2+-free perfusate caused a larger increase of f-I curve slope than apamin or Cd2+, suggesting that the fast transient current may also influence instantaneous firing rate.

Original languageEnglish (US)
Pages (from-to)424-449
Number of pages26
JournalJournal of neurophysiology
Volume59
Issue number2
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Fingerprint Dive into the research topics of 'Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro'. Together they form a unique fingerprint.

  • Cite this