Display options
Cite
Andrade R, Foehring RC, Tzingounis AV. The calcium-activated slow AHP: cutting through the Gordian knot. Front Cell Neurosci. 2012;6:47doi: 10.3389/fncel.2012.00047.
Andrade, R., Foehring, R. C., & Tzingounis, A. V. (2012). The calcium-activated slow AHP: cutting through the Gordian knot. Frontiers in cellular neuroscience, 647. https://doi.org/10.3389/fncel.2012.00047
Andrade, Rodrigo, et al. "The calcium-activated slow AHP: cutting through the Gordian knot." Frontiers in cellular neuroscience vol. 6 (2012): 47. doi: https://doi.org/10.3389/fncel.2012.00047
Andrade R, Foehring RC, Tzingounis AV. The calcium-activated slow AHP: cutting through the Gordian knot. Front Cell Neurosci. 2012 Oct 25;6:47. doi: 10.3389/fncel.2012.00047. eCollection 2012. PMID: 23112761; PMCID: PMC3480710.
Copy Download .nbib Format: NLM
Share it on

Front Cell Neurosci. 2012 Oct 25;6:47. doi: 10.3389/fncel.2012.00047. eCollection 2012.

The calcium-activated slow AHP: cutting through the Gordian knot.

Frontiers in cellular neuroscience

Rodrigo Andrade, Robert C Foehring, Anastasios V Tzingounis

Affiliations

  1. Department of Pharmacology, Wayne State University School of Medicine Detroit, MI, USA.

PMID: 23112761 PMCID: PMC3480710 DOI: 10.3389/fncel.2012.00047

Abstract

The phenomenon known as the slow afterhyperpolarization (sAHP) was originally described more than 30 years ago in pyramidal cells as a slow, Ca(2+)-dependent afterpotential controlling spike frequency adaptation. Subsequent work showed that similar sAHPs were widely expressed in the brain and were mediated by a Ca(2+)-activated potassium current that was voltage-independent, insensitive to most potassium channel blockers, and strongly modulated by neurotransmitters. However, the molecular basis for this current has remained poorly understood. The sAHP was initially imagined to reflect the activation of a potassium channel directly gated by Ca(2+) but recent studies have begun to question this idea. The sAHP is distinct from the Ca(2+)-dependent fast and medium AHPs in that it appears to sense cytoplasmic [Ca(2+)](i) and recent evidence implicates proteins of the neuronal calcium sensor (NCS) family as diffusible cytoplasmic Ca(2+) sensors for the sAHP. Translocation of Ca(2+)-bound sensor to the plasma membrane would then be an intermediate step between Ca(2+) and the sAHP channels. Parallel studies strongly suggest that the sAHP current is carried by different potassium channel types depending on the cell type. Finally, the sAHP current is dependent on membrane PtdIns(4,5)P(2) and Ca(2+) appears to gate this current by increasing PtdIns(4,5)P(2) levels. Because membrane PtdIns(4,5)P(2) is essential for the activity of many potassium channels, these finding have led us to hypothesize that the sAHP reflects a transient Ca(2+)-induced increase in the local availability of PtdIns(4,5)P(2) which then activates a variety of potassium channels. If this view is correct, the sAHP current would not represent a unitary ionic current but the embodiment of a generalized potassium channel gating mechanism. This model can potentially explain the cardinal features of the sAHP, including its cellular heterogeneity, slow kinetics, dependence on cytoplasmic [Ca(2+)], high temperature-dependence, and modulation.

Keywords: Ca2+-activated afterhyperpolarization; KCNQ; PtdIns(4,5)P2; neuromodulation; pyramidal cell; sAHP

References

  1. Brain Res Dev Brain Res. 1995 Feb 16;84(2):192-203 - PubMed
  2. Br J Pharmacol. 2001 Feb;132(4):889-98 - PubMed
  3. Nature. 2011 Aug 28;477(7365):495-8 - PubMed
  4. J Physiol. 2005 Jul 15;566(Pt 2):505-18 - PubMed
  5. J Neurophysiol. 1998 Nov;80(5):2268-73 - PubMed
  6. J Neurosci. 1999 May 15;19(10):3657-64 - PubMed
  7. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4662-7 - PubMed
  8. J Physiol. 1992 Oct;456:325-49 - PubMed
  9. Nat Rev Neurosci. 2006 Dec;7(12):921-31 - PubMed
  10. J Comput Neurosci. 1998 Jul;5(3):331-48 - PubMed
  11. J Neurosci. 1984 Jan;4(1):161-70 - PubMed
  12. J Physiol. 2000 Sep 1;527 Pt 2:249-64 - PubMed
  13. Neuron. 1991 Aug;7(2):257-64 - PubMed
  14. Neuroscience. 1992;47(3):571-8 - PubMed
  15. Brain Res. 1984 Jul 9;305(2):283-90 - PubMed
  16. J Neurosci. 2009 Jul 1;29(26):8396-407 - PubMed
  17. J Physiol. 1987 Aug;389:187-203 - PubMed
  18. J Gen Physiol. 2009 Nov;134(5):437-48 - PubMed
  19. Science. 1980 Dec 5;210(4474):1125-6 - PubMed
  20. J Neurophysiol. 1992 Feb;67(2):350-63 - PubMed
  21. J Neurophysiol. 2000 Apr;83(4):2071-9 - PubMed
  22. Science. 1998 Nov 6;282(5391):1141-4 - PubMed
  23. Nat Rev Neurosci. 2007 Mar;8(3):182-93 - PubMed
  24. J Neurophysiol. 2005 Apr;93(4):2012-20 - PubMed
  25. Science. 2004 Apr 9;304(5668):265-70 - PubMed
  26. J Physiol. 1994 Mar 1;475(2):229-39 - PubMed
  27. Prog Neurobiol. 2002 Apr;66(5):345-53 - PubMed
  28. J Gen Physiol. 1998 Apr;111(4):565-81 - PubMed
  29. Biophys J. 2010 Aug 9;99(4):1110-8 - PubMed
  30. Prog Brain Res. 1990;83:161-87 - PubMed
  31. J Physiol. 1997 Feb 15;499 ( Pt 1):121-34 - PubMed
  32. Neurosci Lett. 2008 Sep 12;442(2):152-7 - PubMed
  33. Science. 1998 Nov 6;282(5391):1138-41 - PubMed
  34. J Neurosci. 2011 Dec 14;31(50):18303-12 - PubMed
  35. J Gen Physiol. 2010 Feb;135(2):99-114 - PubMed
  36. Nat Rev Neurosci. 2005 Nov;6(11):850-62 - PubMed
  37. J Neurosci. 2005 Nov 2;25(44):10230-8 - PubMed
  38. J Physiol. 1989 Feb;409:171-90 - PubMed
  39. Science. 1980 Dec 5;210(4474):1122-4 - PubMed
  40. J Neurophysiol. 1992 Dec;68(6):2100-9 - PubMed
  41. Br J Pharmacol. 2000 Feb;129(4):627-30 - PubMed
  42. J Pharmacol Exp Ther. 1998 Aug;286(2):709-17 - PubMed
  43. J Neurophysiol. 1997 Aug;78(2):825-34 - PubMed
  44. J Neurophysiol. 1988 Mar;59(3):978-96 - PubMed
  45. Biophys J. 2000 May;78(5):2655-67 - PubMed
  46. Biophys J. 2000 May;78(5):2334-48 - PubMed
  47. Neuron. 1998 Mar;20(3):389-99 - PubMed
  48. Eur J Neurosci. 2003 Dec;18(12):3155-66 - PubMed
  49. J Neurosci. 1987 Mar;7(3):733-41 - PubMed
  50. Neuroscience. 1991;40(2):399-412 - PubMed
  51. Circ Res. 2005 Apr 15;96(7):730-9 - PubMed
  52. J Neurophysiol. 2011 Oct;106(4):1722-33 - PubMed
  53. Br J Pharmacol. 1995 Aug;115(7):1163-8 - PubMed
  54. J Neurosci. 2010 Oct 27;30(43):14361-5 - PubMed
  55. J Neurophysiol. 1995 Dec;74(6):2749-53 - PubMed
  56. Mol Pharmacol. 1996 Nov;50(5):1316-22 - PubMed
  57. J Neurophysiol. 1998 Jan;79(1):217-26 - PubMed
  58. J Neurophysiol. 1992 Nov;68(5):1834-41 - PubMed
  59. J Neurosci. 1988 Nov;8(11):4214-24 - PubMed
  60. Ann N Y Acad Sci. 1999 Apr 30;868:233-85 - PubMed
  61. J Neurosci. 1991 Jan;11(1):23-30 - PubMed
  62. Neuroreport. 1999 Jun 23;10(9):1951-6 - PubMed
  63. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10232-7 - PubMed
  64. J Neurosci. 2006 Aug 23;26(34):8787-99 - PubMed
  65. J Neurosci. 2001 Oct 15;21(20):RC175 - PubMed
  66. J Neurophysiol. 1995 Dec;74(6):2225-41 - PubMed
  67. J Physiol. 1982 Aug;329:341-54 - PubMed
  68. Pflugers Arch. 2004 May;448(2):187-96 - PubMed
  69. J Biol Chem. 2001 Feb 16;276(7):4781-7 - PubMed
  70. J Neurophysiol. 1988 Feb;59(2):424-49 - PubMed
  71. Neuron. 1995 Aug;15(2):435-41 - PubMed
  72. J Auton Nerv Syst. 1993 Mar;42(3):251-7 - PubMed
  73. J Neurophysiol. 1988 Feb;59(2):450-67 - PubMed
  74. J Physiol. 1983 Apr;337:287-301 - PubMed
  75. Neuroscience. 1984 Sep;13(1):137-56 - PubMed
  76. J Neurosci. 2004 Jun 9;24(23):5301-6 - PubMed
  77. Cell Mol Life Sci. 2008 Oct;65(20):3196-217 - PubMed
  78. Brain Res. 1987 Dec 1;435(1-2):387-92 - PubMed
  79. J Neurosci. 1997 Sep 1;17(17):6493-503 - PubMed
  80. Mol Pharmacol. 2006 Nov;70(5):1494-502 - PubMed
  81. Science. 1996 Sep 20;273(5282):1709-14 - PubMed
  82. J Neurophysiol. 1993 Jun;69(6):2150-63 - PubMed
  83. Nature. 1983 Mar 31-Apr 6;302(5907):432-4 - PubMed
  84. J Neurophysiol. 2000 Sep;84(3):1346-54 - PubMed
  85. J Neurosci. 2007 Jan 17;27(3):483-95 - PubMed
  86. Brain Res Dev Brain Res. 1993 Jun 8;73(2):213-23 - PubMed
  87. Biophys J. 1996 Feb;70(2):1069-81 - PubMed
  88. Neuron. 2008 Sep 25;59(6):873-81 - PubMed
  89. J Physiol. 2005 Jul 15;566(Pt 2):519-32 - PubMed
  90. Annu Rev Biophys Bioeng. 1978;7:1-18 - PubMed
  91. J Neurophysiol. 2000 May;83(5):2554-61 - PubMed
  92. J Neurophysiol. 1980 Feb;43(2):409-19 - PubMed
  93. Brain Res. 1981 Feb 16;206(2):462-8 - PubMed
  94. Nat Rev Neurosci. 2007 Jun;8(6):451-65 - PubMed
  95. J Neurophysiol. 1989 Feb;61(2):245-56 - PubMed
  96. Brain Res. 1984 Dec 17;324(1):180-4 - PubMed
  97. Hippocampus. 2011 Feb;21(2):133-41 - PubMed
  98. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19974-9 - PubMed
  99. J Neurosci. 2011 Jun 8;31(23):8689-96 - PubMed
  100. Eur J Neurosci. 2005 Sep;22(5):1120-6 - PubMed
  101. Pharmacol Ther. 2006 Apr;110(1):103-16 - PubMed
  102. Neuron. 2008 Aug 14;59(3):439-49 - PubMed
  103. J Physiol. 2005 Aug 1;566(Pt 3):689-715 - PubMed
  104. Nature. 1990 Oct 25;347(6295):765-7 - PubMed
  105. J Neurophysiol. 2001 May;85(5):1941-51 - PubMed
  106. J Neurophysiol. 2008 Nov;100(5):2589-604 - PubMed
  107. J Neurophysiol. 1995 Oct;74(4):1772-6 - PubMed
  108. J Neurophysiol. 1989 Feb;61(2):233-44 - PubMed
  109. Nature. 1998 Oct 1;395(6701):503-7 - PubMed
  110. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8098-102 - PubMed
  111. Neuron. 1992 Aug;9(2):209-16 - PubMed
  112. J Physiol. 1996 Sep 1;495 ( Pt 2):353-66 - PubMed
  113. J Neurophysiol. 1998 May;79(5):2522-34 - PubMed
  114. J Neurosci. 2002 Feb 1;22(3):666-73 - PubMed
  115. J Physiol. 2006 Oct 15;576(Pt 2):403-17 - PubMed
  116. J Neurophysiol. 1992 Jul;68(1):287-94 - PubMed
  117. J Neurosci. 2010 May 5;30(18):6214-24 - PubMed
  118. Mol Pharmacol. 2010 Dec;78(6):1088-95 - PubMed
  119. J Gen Physiol. 2007 Sep;130(3):241-56 - PubMed
  120. Neuroscience. 1999;88(3):719-26 - PubMed
  121. EMBO J. 2003 Oct 15;22(20):5412-21 - PubMed
  122. Neuron. 2007 Feb 15;53(4):487-93 - PubMed
  123. J Neurophysiol. 1998 Jun;79(6):3252-6 - PubMed
  124. Nature. 1982 Oct 14;299(5884):636-8 - PubMed
  125. Neuron. 1993 Dec;11(6):1023-35 - PubMed
  126. J Physiol. 1987 Jun;387:173-94 - PubMed
  127. J Neurosci. 2004 Apr 7;24(14):3537-42 - PubMed
  128. J Comput Neurosci. 1999 May-Jun;6(3):215-35 - PubMed
  129. Proc Natl Acad Sci U S A. 1985 May;82(9):3040-4 - PubMed
  130. Brain Res. 1982 Oct 14;249(2):315-31 - PubMed
  131. J Neurophysiol. 1992 Jan;67(1):216-26 - PubMed
  132. J Neurophysiol. 2000 May;83(5):3084-100 - PubMed
  133. J Physiol. 1999 May 15;517 ( Pt 1):201-16 - PubMed
  134. J Neurophysiol. 1986 Jun;55(6):1268-82 - PubMed
  135. Pflugers Arch. 2001 Jan;441(4):544-50 - PubMed
  136. J Physiol. 1984 Sep;354:319-31 - PubMed
  137. J Neurophysiol. 2004 Jan;91(1):324-35 - PubMed
  138. Mol Pharmacol. 1995 Jan;47(1):191-7 - PubMed
  139. J Neurosci. 1994 Feb;14(2):523-37 - PubMed
  140. J Physiol. 1987 Dec;394:99-124 - PubMed
  141. J Cell Biol. 2003 Nov 24;163(4):715-21 - PubMed
  142. Neuron. 1996 Jan;16(1):151-62 - PubMed
  143. J Gen Physiol. 2003 Jul;122(1):17-31 - PubMed
  144. J Neurophysiol. 2009 Jun;101(6):2741-50 - PubMed
  145. Prog Neurobiol. 2010 Jul;91(3):242-55 - PubMed

Publication Types

Grant support