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. 1993 Jun;465:265–287. doi: 10.1113/jphysiol.1993.sp019676

Large conductance Ca(2+)-activated K+ channels are involved in both spike shaping and firing regulation in Helix neurones.

M Crest 1, M Gola 1
PMCID: PMC1175429  PMID: 8229836

Abstract

1. The role of BK-type calcium-dependent K+ channels (K+Ca) in cell firing regulation was evaluated by performing whole-cell voltage clamp and patch clamp experiments on the U cell neurones in the snail Helix pomatia. These cells were selected because most of the repolarizing K+ current flowed through K+Ca channels. 2. U cells generated overshooting Ca(2+)-dependent spikes in Na(+)-free saline. In response to prolonged depolarizing current, they fired a limited number of spikes of decreasing amplitude, and behaved like fast-adapting or phasic neurones. 3. Under voltage clamp conditions, the K+Ca current had a slow onset at voltages that induced small Ca2+ entries. By manipulating the Ca2+ entry (either with appropriate voltage programmes or by changing the Ca2+ content of the bath), the K+Ca channel opening was found to be rate limited by the Ca2+ binding step and not by the voltage-dependent conformational change to the open state. 4. Despite the slow activation rate observed in voltage-clamped cells, 25-30% of the available K+Ca current was found to be active during isolated spikes. These data were based on patch clamp, spike-like voltage clamp and hybrid current clamp-voltage clamp experiments. 5. The fact that spikes led the slowly rising K+Ca current to shift into a fast activating mode was accounted for by the large surge of Ca2+ current concomitant with spike upstroke. The early calcium surge resulted in local increases in cytosolic calcium, which speeded up the binding of calcium ions to the closed K+Ca channels. From changes in the null Ca2+ current voltage, it was calculated that the submembrane [Ca2+]i increase to 50-80 microM during the spike. 6. Due to their fast voltage dependence, K+Ca channels appeared to play no role in shaping the interspike trajectory. 7. Even in the fast activating mode, the K+Ca current had a finite rate of rise and was not involved in repolarizing short duration Na(+-dependent action potentials. The current became more and more active, however, when voltage-gated K+ channels were progressively inactivated during firing. 8. The fast adaptation exhibited by U cells upon sustained depolarization was not paralleled by a recruitment of K+Ca channels because of the cumulative Ca2+ entries. During a spike burst, the K+Ca current progressively overlapped the depolarizing Ca2+ current, which ultimately stopped the firing. The early opening of K+Ca channels was ascribed to residual Ca2+ accumulation that kept part of the channels in the Ca(2+)-bound state ready to be opened quickly by cell depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Adams P. R., Constanti A., Brown D. A., Clark R. B. Intracellular Ca2+ activates a fast voltage-sensitive K+ current in vertebrate sympathetic neurones. Nature. 1982 Apr 22;296(5859):746–749. doi: 10.1038/296746a0. [DOI] [PubMed] [Google Scholar]
  2. Adler E. M., Augustine G. J., Duffy S. N., Charlton M. P. Alien intracellular calcium chelators attenuate neurotransmitter release at the squid giant synapse. J Neurosci. 1991 Jun;11(6):1496–1507. doi: 10.1523/JNEUROSCI.11-06-01496.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alger B. E., Williamson A. A transient calcium-dependent potassium component of the epileptiform burst after-hyperpolarization in rat hippocampus. J Physiol. 1988 May;399:191–205. doi: 10.1113/jphysiol.1988.sp017075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Belardetti F., Schacher S., Siegelbaum S. A. Action potentials, macroscopic and single channel currents recorded from growth cones of Aplysia neurones in culture. J Physiol. 1986 May;374:289–313. doi: 10.1113/jphysiol.1986.sp016080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bezanilla F., Rojas E., Taylor R. E. Sodium and potassium conductance changes during a membrane action potential. J Physiol. 1970 Dec;211(3):729–751. doi: 10.1113/jphysiol.1970.sp009301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brett R. S., Dilger J. P., Adams P. R., Lancaster B. A method for the rapid exchange of solutions bathing excised membrane patches. Biophys J. 1986 Nov;50(5):987–992. doi: 10.1016/S0006-3495(86)83539-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crest M., Jacquet G., Gola M., Zerrouk H., Benslimane A., Rochat H., Mansuelle P., Martin-Eauclaire M. F. Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom. J Biol Chem. 1992 Jan 25;267(3):1640–1647. [PubMed] [Google Scholar]
  8. Deitmer J. W., Eckert R. Two components of Ca-dependent potassium current in identified neurons of Aplysia californica. Pflugers Arch. 1985 Apr;403(4):353–359. doi: 10.1007/BF00589246. [DOI] [PubMed] [Google Scholar]
  9. Delaney K. R., Zucker R. S., Tank D. W. Calcium in motor nerve terminals associated with posttetanic potentiation. J Neurosci. 1989 Oct;9(10):3558–3567. doi: 10.1523/JNEUROSCI.09-10-03558.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dryer S. E., Dourado M. M., Wisgirda M. E. Characteristics of multiple Ca(2+)-activated K+ channels in acutely dissociated chick ciliary-ganglion neurones. J Physiol. 1991 Nov;443:601–627. doi: 10.1113/jphysiol.1991.sp018854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eckert R., Tillotson D. Potassium activation associated with intraneuronal free calcium. Science. 1978 Apr 28;200(4340):437–439. doi: 10.1126/science.644308. [DOI] [PubMed] [Google Scholar]
  12. Galvan M., Sedlmeir C. Outward currents in voltage-clamped rat sympathetic neurones. J Physiol. 1984 Nov;356:115–133. doi: 10.1113/jphysiol.1984.sp015456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gola M., Ducreux C., Chagneux H. Ca2(+)-activated K+ current involvement in neuronal function revealed by in situ single-channel analysis in Helix neurones. J Physiol. 1990 Jan;420:73–109. doi: 10.1113/jphysiol.1990.sp017902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gola M., Hussy N., Crest M., Ducreux C. Time course of Ca and Ca-dependent K currents during molluscan nerve cell action potentials. Neurosci Lett. 1986 Oct 20;70(3):354–359. doi: 10.1016/0304-3940(86)90578-1. [DOI] [PubMed] [Google Scholar]
  15. Gorman A. L., Hermann A., Thomas M. V. Intracellular calcium and the control of neuronal pacemaker activity. Fed Proc. 1981 Jun;40(8):2233–2239. [PubMed] [Google Scholar]
  16. Gorman A. L., Thomas M. V. Potassium conductance and internal calcium accumulation in a molluscan neurone. J Physiol. 1980 Nov;308:287–313. doi: 10.1113/jphysiol.1980.sp013472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hounsgaard J., Mintz I. Calcium conductance and firing properties of spinal motoneurones in the turtle. J Physiol. 1988 Apr;398:591–603. doi: 10.1113/jphysiol.1988.sp017059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ikemoto Y., Ono K., Yoshida A., Akaike N. Delayed activation of large-conductance Ca2+-activated K channels in hippocampal neurons of the rat. Biophys J. 1989 Jul;56(1):207–212. doi: 10.1016/S0006-3495(89)82665-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johansen J., Yang J., Kleinhaus A. L. Voltage-clamp analysis of the ionic conductances in a leech neuron with a purely calcium-dependent action potential. J Neurophysiol. 1987 Dec;58(6):1468–1484. doi: 10.1152/jn.1987.58.6.1468. [DOI] [PubMed] [Google Scholar]
  20. KEYNES R. D., LEWIS P. R. The sodium and potassium content of cephalopod nerve fibers. J Physiol. 1951 Jun;114(1-2):151–182. doi: 10.1113/jphysiol.1951.sp004609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kawai T., Watanabe M. Blockade of Ca-activated K conductance by apamin in rat sympathetic neurones. Br J Pharmacol. 1986 Jan;87(1):225–232. doi: 10.1111/j.1476-5381.1986.tb10175.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kostyuk P. G., Doroshenko P. A., Tsyndrenko A. Y. Calcium-dependent potassium conductance studied on internally dialysed nerve cells. Neuroscience. 1980;5(12):2187–2192. doi: 10.1016/0306-4522(80)90135-9. [DOI] [PubMed] [Google Scholar]
  23. Lancaster B., Adams P. R. Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J Neurophysiol. 1986 Jun;55(6):1268–1282. doi: 10.1152/jn.1986.55.6.1268. [DOI] [PubMed] [Google Scholar]
  24. Lancaster B., Nicoll R. A., Perkel D. J. Calcium activates two types of potassium channels in rat hippocampal neurons in culture. J Neurosci. 1991 Jan;11(1):23–30. doi: 10.1523/JNEUROSCI.11-01-00023.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lang D. G., Ritchie A. K. Large and small conductance calcium-activated potassium channels in the GH3 anterior pituitary cell line. Pflugers Arch. 1987 Dec;410(6):614–622. doi: 10.1007/BF00581321. [DOI] [PubMed] [Google Scholar]
  26. Lang D. G., Ritchie A. K. Tetraethylammonium blockade of apamin-sensitive and insensitive Ca2(+)-activated K+ channels in a pituitary cell line. J Physiol. 1990 Jun;425:117–132. doi: 10.1113/jphysiol.1990.sp018095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Llinás R., Steinberg I. Z., Walton K. Presynaptic calcium currents in squid giant synapse. Biophys J. 1981 Mar;33(3):289–321. doi: 10.1016/S0006-3495(81)84898-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Llinás R., Sugimori M., Silver R. B. Microdomains of high calcium concentration in a presynaptic terminal. Science. 1992 May 1;256(5057):677–679. doi: 10.1126/science.1350109. [DOI] [PubMed] [Google Scholar]
  29. Llinás R., Sugimori M., Simon S. M. Transmission by presynaptic spike-like depolarization in the squid giant synapse. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2415–2419. doi: 10.1073/pnas.79.7.2415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lux H. D., Hofmeier G. Activation characteristics of the calcium-dependent outward potassium current in Helix. Pflugers Arch. 1982 Jul;394(1):70–77. doi: 10.1007/BF01108310. [DOI] [PubMed] [Google Scholar]
  31. MacDermott A. B., Weight F. F. Action potential repolarization may involve a transient, Ca2+-sensitive outward current in a vertebrate neurone. Nature. 1982 Nov 11;300(5888):185–188. doi: 10.1038/300185a0. [DOI] [PubMed] [Google Scholar]
  32. Madison D. V., Nicoll R. A. Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J Physiol. 1984 Sep;354:319–331. doi: 10.1113/jphysiol.1984.sp015378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. McManus O. B. Calcium-activated potassium channels: regulation by calcium. J Bioenerg Biomembr. 1991 Aug;23(4):537–560. doi: 10.1007/BF00785810. [DOI] [PubMed] [Google Scholar]
  34. Mosfeldt Laursen A., Rekling J. C. Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro. Neuroscience. 1989;30(3):619–637. doi: 10.1016/0306-4522(89)90156-5. [DOI] [PubMed] [Google Scholar]
  35. Müller T. H., Swandulla D., Lux H. D. Activation of three types of membrane currents by various divalent cations in identified molluscan pacemaker neurons. J Gen Physiol. 1989 Dec;94(6):997–1014. doi: 10.1085/jgp.94.6.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Müller W., Connor J. A. Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses. Nature. 1991 Nov 7;354(6348):73–76. doi: 10.1038/354073a0. [DOI] [PubMed] [Google Scholar]
  37. Reinhart P. H., Chung S., Levitan I. B. A family of calcium-dependent potassium channels from rat brain. Neuron. 1989 Jan;2(1):1031–1041. doi: 10.1016/0896-6273(89)90227-4. [DOI] [PubMed] [Google Scholar]
  38. Ritchie A. K. Two distinct calcium-activated potassium currents in a rat anterior pituitary cell line. J Physiol. 1987 Apr;385:591–609. doi: 10.1113/jphysiol.1987.sp016509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smart T. G. Single calcium-activated potassium channels recorded from cultured rat sympathetic neurones. J Physiol. 1987 Aug;389:337–360. doi: 10.1113/jphysiol.1987.sp016660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Storm J. F. Intracellular injection of a Ca2+ chelator inhibits spike repolarization in hippocampal neurons. Brain Res. 1987 Dec 1;435(1-2):387–392. doi: 10.1016/0006-8993(87)91631-3. [DOI] [PubMed] [Google Scholar]
  41. Tsien R. Y. Fluorescence measurement and photochemical manipulation of cytosolic free calcium. Trends Neurosci. 1988 Oct;11(10):419–424. doi: 10.1016/0166-2236(88)90192-0. [DOI] [PubMed] [Google Scholar]
  42. Woolum J. C., Gorman A. L. Time dependence of the calcium-activated potassium current. Biophys J. 1981 Oct;36(1):297–302. doi: 10.1016/S0006-3495(81)84729-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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