Journal of Neurophysiology, Vol 43, Issue 2 409-419, Copyright © 1980 by APS

ARTICLES

A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons

J. R. Hotson and D. A. Prince

1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.

This article has been cited by other articles:

				M. M. Shah, M. Migliore, I. Valencia, E. C. Cooper, and D. A. Brown Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons PNAS, June 3, 2008; 105(22): 7869 - 7874. [Abstract] [Full Text] [PDF]

				P. M. Sonner and J. E. Stern Functional role of A-type potassium currents in rat presympathetic PVN neurones J. Physiol., August 1, 2007; 582(3): 1219 - 1238. [Abstract] [Full Text] [PDF]

				J. A. Goldberg and C. J. Wilson Control of Spontaneous Firing Patterns by the Selective Coupling of Calcium Currents to Calcium-Activated Potassium Currents in Striatal Cholinergic Interneurons J. Neurosci., November 2, 2005; 25(44): 10230 - 10238. [Abstract] [Full Text] [PDF]

				H. Li, A. E. Bandrowski, and D. A. Prince Cortical Injury Affects Short-Term Plasticity of Evoked Excitatory Synaptic Currents J Neurophysiol, January 1, 2005; 93(1): 146 - 156. [Abstract] [Full Text] [PDF]

				A. Fisahn, S. F. Heinemann, and C. J. McBain The kainate receptor subunit GluR6 mediates metabotropic regulation of the slow and medium AHP currents in mouse hippocampal neurones J. Physiol., January 1, 2005; 562(1): 199 - 203. [Abstract] [Full Text] [PDF]

				W. W. Wu, C. S. Chan, and J. F. Disterhoft Slow Afterhyperpolarization Governs the Development of NMDA Receptor-Dependent Afterdepolarization in CA1 Pyramidal Neurons During Synaptic Stimulation J Neurophysiol, October 1, 2004; 92(4): 2346 - 2356. [Abstract] [Full Text] [PDF]

				J. Maylie, C. T. Bond, P. S. Herson, W.-S. Lee, and J. P. Adelman Small conductance Ca2+-activated K+ channels and calmodulin J. Physiol., January 15, 2004; 554(2): 255 - 261. [Abstract] [Full Text] [PDF]

				S. R. Young, S.-C. Chuang, and R. K. S. Wong Modulation of afterpotentials and firing pattern in guinea pig CA3 neurones by group I metabotropic glutamate receptors J. Physiol., January 15, 2004; 554(2): 371 - 385. [Abstract] [Full Text] [PDF]

				C. M. McDermott, G. J. LaHoste, C. Chen, A. Musto, N. G. Bazan, and J. C. Magee Sleep Deprivation Causes Behavioral, Synaptic, and Membrane Excitability Alterations in Hippocampal Neurons J. Neurosci., October 22, 2003; 23(29): 9687 - 9695. [Abstract] [Full Text] [PDF]

				C. W. Shuttleworth, A. M. Brennan, and J. A. Connor NAD(P)H Fluorescence Imaging of Postsynaptic Neuronal Activation in Murine Hippocampal Slices J. Neurosci., April 15, 2003; 23(8): 3196 - 3208. [Abstract] [Full Text] [PDF]

				C. A. Sailer, H. Hu, W. A. Kaufmann, M. Trieb, C. Schwarzer, J. F. Storm, and H.-G. Knaus Regional Differences in Distribution and Functional Expression of Small-Conductance Ca2+-Activated K+ Channels in Rat Brain J. Neurosci., November 15, 2002; 22(22): 9698 - 9707. [Abstract] [Full Text] [PDF]

				G. Fuhrmann, H. Markram, and M. Tsodyks Spike Frequency Adaptation and Neocortical Rhythms J Neurophysiol, August 1, 2002; 88(2): 761 - 770. [Abstract] [Full Text] [PDF]

				T. K. Knott, A. M. Dopico, G. Dayanithi, J. Lemos, and S. N. Treistman Integrated Channel Plasticity Contributes to Alcohol Tolerance in Neurohypophysial Terminals Mol. Pharmacol., July 1, 2002; 62(1): 135 - 142. [Abstract] [Full Text] [PDF]

				R. J. Cormier, A. C. Greenwood, and J. A. Connor Bidirectional Synaptic Plasticity Correlated With the Magnitude of Dendritic Calcium Transients Above a Threshold J Neurophysiol, January 1, 2001; 85(1): 399 - 406. [Abstract] [Full Text] [PDF]

				J. R. Moyer Jr, J. M. Power, L. T. Thompson, and J. F. Disterhoft Increased Excitability of Aged Rabbit CA1 Neurons after Trace Eyeblink Conditioning J. Neurosci., July 15, 2000; 20(14): 5476 - 5482. [Abstract] [Full Text] [PDF]

				T. Haug and J. F. Storm Protein Kinase A Mediates the Modulation of the Slow Ca2+-Dependent K+ Current, IsAHP, by the Neuropeptides CRF, VIP, and CGRP in Hippocampal Pyramidal Neurons J Neurophysiol, April 1, 2000; 83(4): 2071 - 2079. [Abstract] [Full Text] [PDF]

				M. Bikson, R. S. Ghai, S. C. Baraban, and D. M. Durand Modulation of Burst Frequency, Duration, and Amplitude in the Zero-Ca2+ Model of Epileptiform Activity J Neurophysiol, November 1, 1999; 82(5): 2262 - 2270. [Abstract] [Full Text] [PDF]

				V. Lopantsev and P. A. Schwartzkroin GABAA-Dependent Chloride Influx Modulates GABAB-Mediated IPSPs in Hippocampal Pyramidal Cells J Neurophysiol, September 1, 1999; 82(3): 1218 - 1223. [Abstract] [Full Text] [PDF]

				J. A. Connor, S. Razani-Boroujerdi, A. C. Greenwood, R. J. Cormier, J. J. Petrozzino, and R. C. S. Lin Reduced Voltage-Dependent Ca2+ Signaling in CA1 Neurons After Brief Ischemia in Gerbils J Neurophysiol, January 1, 1999; 81(1): 299 - 306. [Abstract] [Full Text] [PDF]

				M. Tanabe, B. H. Gahwiler, and U. Gerber L-Type Ca2+ Channels Mediate the Slow Ca2+-Dependent Afterhyperpolarization Current in Rat CA3 Pyramidal Cells In Vitro J Neurophysiol, November 1, 1998; 80(5): 2268 - 2273. [Abstract] [Full Text] [PDF]

				R. A. Chitwood and D. B. Jaffe Calcium-Dependent Spike-Frequency Accommodation in Hippocampal CA3 Nonpyramidal Neurons J Neurophysiol, August 1, 1998; 80(2): 983 - 988. [Abstract] [Full Text] [PDF]

				P. Pedarzani, M. Krause, T. Haug, J. F. Storm, and W. Stuhmer Modulation of the Ca2+-Activated K+ Current sIAHP by aPhosphatase-Kinase Balance Under Basal Conditions inRat CA1 Pyramidal Neurons J Neurophysiol, June 1, 1998; 79(6): 3252 - 3256. [Abstract] [Full Text] [PDF]

				A. Kamondi, L. Acsady, and G. Buzsaki Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus J. Neurosci., May 15, 1998; 18(10): 3919 - 3928. [Abstract] [Full Text] [PDF]

				X.-m. Xia, B. Hirschberg, S. Smolik, M. Forte, and J. P. Adelman dSLo Interacting Protein 1, a Novel Protein That Interacts with Large-Conductance Calcium-Activated Potassium Channels J. Neurosci., April 1, 1998; 18(7): 2360 - 2369. [Abstract] [Full Text] [PDF]

				X.-J. Wang Calcium Coding and Adaptive Temporal Computation in Cortical Pyramidal Neurons J Neurophysiol, March 1, 1998; 79(3): 1549 - 1566. [Abstract] [Full Text] [PDF]

				T. M. Ishii, J. Maylie, and J. P. Adelman Determinants of Apamin and d-Tubocurarine Block in SK Potassium Channels J. Biol. Chem., September 12, 1997; 272(37): 23195 - 23200. [Abstract] [Full Text] [PDF]

				E. Pan and J. L. Stringer Role of Potassium and Calcium in the Generation of Cellular Bursts in the Dentate Gyrus J Neurophysiol, May 1, 1997; 77(5): 2293 - 2299. [Abstract] [Full Text] [PDF]

				J. R. Moyer Jr., L. T. Thompson, and J. F. Disterhoft Trace Eyeblink Conditioning Increases CA1 Excitability in a Transient and Learning-Specific Manner J. Neurosci., September 1, 1996; 16(17): 5536 - 5546. [Abstract] [Full Text] [PDF]

				P. Sah and J. M. Bekkers Apical Dendritic Location of Slow Afterhyperpolarization Current in Hippocampal Pyramidal Neurons: Implications for the Integration of Long-Term Potentiation J. Neurosci., August 1, 1996; 16(15): 4537 - 4542. [Abstract] [Full Text] [PDF]

				M Joels and E. de Kloet Effects of glucocorticoids and norepinephrine on the excitability in the hippocampus Science, September 29, 1989; 245(4925): 1502 - 1505. [Abstract] [PDF]

				D. Kerr, L. Campbell, S. Hao, and P. Landfield Corticosteroid modulation of hippocampal potentials: increased effect with aging Science, September 29, 1989; 245(4925): 1505 - 1509. [Abstract] [PDF]

				R. Nicoll The coupling of neurotransmitter receptors to ion channels in the brain Science, July 29, 1988; 241(4865): 545 - 551. [Abstract] [PDF]

				M. Dichter and G. Ayala Cellular mechanisms of epilepsy: a status report Science, July 10, 1987; 237(4811): 157 - 164. [Abstract] [PDF]

				Y Yaari, B Hamon, and H. Lux Development of two types of calcium channels in cultured mammalian hippocampal neurons Science, February 6, 1987; 235(4789): 680 - 682. [Abstract] [PDF]

				R. Greene, H. Haas, and R. McCarley A low threshold calcium spike mediates firing pattern alterations in pontine reticular neurons Science, November 7, 1986; 234(4777): 738 - 740. [Abstract] [PDF]

				U Misgeld, R. Deisz, H. Dodt, and H. Lux The role of chloride transport in postsynaptic inhibition of hippocampal neurons Science, June 13, 1986; 232(4756): 1413 - 1415. [Abstract] [PDF]

				P. Landfield and T. Pitler Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats Science, November 30, 1984; 226(4678): 1089 - 1092. [Abstract] [PDF]

				D Durand and P. Carlen Decreased neuronal inhibition in vitro after long-term administration of ethanol Science, June 22, 1984; 224(4655): 1359 - 1361. [Abstract] [PDF]

				A. Cole and R. Nicoll Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells Science, September 23, 1983; 221(4617): 1299 - 1301. [Abstract] [PDF]

				J. Aldenhoff, D. Gruol, J Rivier, W Vale, and G. Siggins Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons Science, August 26, 1983; 221(4613): 875 - 877. [Abstract] [PDF]

				R Eckert and D Ewald Residual calcium ions depress activation of calcium-dependent current Science, May 14, 1982; 216(4547): 730 - 733. [Abstract] [PDF]

				R. Traub and R. Wong Cellular mechanism of neuronal synchronization in epilepsy Science, May 14, 1982; 216(4547): 745 - 747. [Abstract] [PDF]

				G. Aghajanian and C. VanderMaelen alpha 2-adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: intracellular studies in vivo Science, March 12, 1982; 215(4538): 1394 - 1396. [Abstract] [PDF]

				P. Carlen, N Gurevich, and D Durand Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons Science, January 15, 1982; 215(4530): 306 - 309. [Abstract] [PDF]

				R. Nicoll and B. Alger Synaptic excitation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells Science, May 22, 1981; 212(4497): 957 - 959. [Abstract] [PDF]

				B. Alger and R. Nicoll Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells Science, December 5, 1980; 210(4474): 1122 - 1124. [Abstract] [PDF]

				P. Schwartzkroin and C. Stafstrom Effects of EGTA on the calcium-activated afterhyperpolarization in hippocampal CA3 pyramidal cells Science, December 5, 1980; 210(4474): 1125 - 1126. [Abstract] [PDF]