Skip to main content
Log in

K+ channels in PC12 cells are affected by propofol

  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The effect on K+ currents (I K) of the general anaesthetic propofol (PR) (2,6-diisopropylphenol) was tested in undifferentiated clonal pheochromocytoma (PC12) cells using the patch-clamp technique in whole-cell and single-channel configurations. PR decreased macroscopic I K amplitudes in a concentration-dependent way from 50 μM to 1 mM. The blocking effect was unchanged by repetitive depolarizing pulses and it was independent of the holding potential. Whereas activation of I K in control conditions was fitted by sigmoidal plus exponential time courses, only the sigmoidal time course gave an adequate fit with PR in the bath. The above effects were reversible. PR concentrations below 140 μM decreased single-channel activity for K+ channels with unitary conductance of 22 pS, in the voltage range between −40 and 60 mV from a holding potential of −50 mV. In contrast, the anaesthetic had nearly no effect on the opening probability of a channel with conductance of 10 pS. The unitary current amplitudes were unaffected in both channel types. These results suggest that PR action on I K may depend on the different blocking mechanisms of the K+ channels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Armstrong CM (1969) Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. J Gen Physiol 54:553–575

    Google Scholar 

  2. Barker JL, Harrison NL, Lange GD, Owen DG (1987) Potentiation of γ-aminobutyric-acid-activated chloride conductance by a steroid anaesthetic in cultured rat spinal neurones. J Physiol (Lond) 386:485–501

    Google Scholar 

  3. Benoit E, Carratu MR, Dubois JM, Mitolo-Chieppa D (1986) Mechanism of action of ketamine in the current and voltage clamped myelinated nerve fibre of the frog. Br J Pharmacol 87:251–297

    Google Scholar 

  4. Cockshott ID (1985) Propofol (“Diprivan”) Pharmacokinetics and metabolism. An overview. Postgrad Med J 61:3–45

    Google Scholar 

  5. Cook NS (1988) The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci 9:21–28

    Google Scholar 

  6. Doze VA, Chen BX, Maze M (1989) Dexmedetomidine produces a hypnotic anesthetic action in rats via activation of central alpha-2 adrenoceptors. Anesthesiology 71:75–75

    Google Scholar 

  7. Forman SA, Miller KW (1989) Molecular sites of anesthetic action in postsynaptic nicotinic membranes. Trends Pharmacol Sci 10:447–452

    Google Scholar 

  8. Frank NP, Lieb WR (1988) Volatile general anaesthetics activate a novel neuronal K+ current. Nature 333:662–664

    Google Scholar 

  9. Gross RA, MacDonald RL (1988) Differential actions of pentobarbitone on calcium current component of mouse sensory neurones in culture. J Physiol (Lond) 405:187–203

    Google Scholar 

  10. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflügers Arch 91:85–1000

    Google Scholar 

  11. Haydon DA, Requena J, Simon AJB (1988) The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics. J Physiol (Lond) 402:363–374

    Google Scholar 

  12. Higashi H, Nishi S (1982) Effect of barbiturates on the GABA receptor of cat primary afferent neurones. J Physiol (Lond) 332:299–314

    Google Scholar 

  13. Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptors reaction. J Gen Physiol 69:497–515

    Google Scholar 

  14. Hoshi T, Aldrich RW (1988) Voltage-dependent K+ currents and underlying single channels in pheochromocytoma cells. J Gen Physiol 91:73–106

    Google Scholar 

  15. Kasai H, Kameyama M, Yamaguchi K, Fukuda J (1989) Single transient K channels in mammalian sensory neurons. Biophys J 49:1243–1247

    Google Scholar 

  16. Lansman JB, Hess P, Tsien RW (1986) Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. J Gen Physiol 88:321–347

    Google Scholar 

  17. Lodge D, Anis NA (1982) Effects of optical isomers of ketamine on excitation of cat and rat spinal neurons by aminoacids and acetylcholine. Neurosci Lett 29:281–286

    Google Scholar 

  18. MacDonald RL, Rogers CJ, Twyman RE (1989) Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture. J Physiol (Lond) 417:483–500

    Google Scholar 

  19. MacIver MB, Tanellian DL (1991) Volatile anesthetics excite mammalian nociceptor afferents recorded “in vitro”. Anesthesiology 72:1022–1030

    Google Scholar 

  20. Meves H, Pichon Y (1977) The effect of internal an external 4-aminopyridine on the potassium currents in intracellularly perfused squid giant axons. J Physiol (Lond) 268:511–532

    Google Scholar 

  21. Rudy B, Kirschenbaum B, Green LA (1982) Nerve growth factor-induced increase in saxitoxin binding to rat PC12 pheochromocytoma cells. J Neurosci 2:1405–1411

    Google Scholar 

  22. Southan AP, Wann KT (1989) “In vitro” actions of ketamine and methoexitone in the rat hippocampus. Br J Anaesth 63:574–580

    Google Scholar 

  23. Stark RD, Binks SM, Dutka UN, O'Connor KM, Arnstein MJA, Glen JB (1985) A review of the safety and tolerance of propofol (‘Diprivan’). Postgrad Med J 61:152–156

    Google Scholar 

  24. Streit J, Lux HD (1987) Voltage dependent calcium current in PC 12 growth cones and cells during NGF-induced cell growth. Pflügers Arch 408:634–641

    Google Scholar 

  25. Study RE, Barker JL (1981) Diazepan and (−)-pentobarbital: fluctuation ssanalysis reveals different mechanisms for potentiation of γ-aminobutyric acid responses in cultured central neurons. Proc Natl Acad Sci USA 78:7180–7184

    Google Scholar 

  26. Yeh JZ, Oxford GS, Wu CH, Narahashi T (1976) Dynamics of aminopyridine block of potassium channels in squid axon membrane. J Gen Physiol 68:519–535

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magnelli, V., Nobile, M. & Maestrone, E. K+ channels in PC12 cells are affected by propofol. Pflügers Arch 420, 393–398 (1992). https://doi.org/10.1007/BF00374475

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00374475

Key words

Navigation