The Journal of Neurophysiology Vol. 79 No. 6 June 1998, pp. 2885-2894
Copyright ©1998 The American Physiological Society

Contribution of Ca²⁺-Activated K⁺ Channels to Central Chemosensitivity in Cultivated Neurons of Fetal Rat Medulla

M.-C. Wellner-Kienitz, H. Shams, and P. Scheid

Institut für Physiologie, Ruhr-Universität Bochum, 44780 Bochum, Germany

Wellner-Kienitz, M.-C., H. Shams, and P. Scheid. Contribution of Ca²⁺-activated K⁺ channels to central chemosensitivity in cultivated neurons of fetal rat medulla. J. Neurophysiol. 79: 2885-2894, 1998. Neurons in fetal rat medullary slices that exhibited spontaneous electrical activity after blockade of synaptic transmission were investigated for their response to decreases in extracellular pH. Increases in [H⁺] (induced either by fixed acid or increases in PCO₂) induced a significant increase in the frequency of action potentials, associated with a membrane depolarization, and/or increases in the slope of the interspike depolarization. In addition, CO₂/H⁺ prolonged the repolarizing phase of action potentials and reduced the afterhyperpolarization, suggesting that K⁺ channels were the primary site of CO₂/H⁺ action. The type of K⁺ channel that was modulated by CO₂/H⁺ was identified by application of agents that inhibited Ca²⁺-activated K⁺ channels either directly (tetraethylammonium chloride, TEA) or indirectly (Cd²⁺ ions) by inhibiting Ca²⁺ influx. CO₂/H⁺ effects on neuronal activity were abolished after application of these blockers. The contribution of Ca²⁺-activated K⁺ channels to H⁺ sensitivity of these neurons was confirmed further in voltage-clamp experiments in which outward rectifying I-V curves were recorded that revealed a zero current potential of 70 mV. CO₂/H⁺ induced a prominent reduction in outward currents and shifted the zero current potential to more positive membrane potentials (mean 63 mV). The CO₂/H⁺-sensitive current reversed at 72 mV and was blocked by external application of TEA. It is concluded that CO₂/H⁺ exerts its stimulatory effects on fetal medullary neurons by inhibition of Ca²⁺-activated K⁺ channels, either directly or indirectly, by blocking voltage-dependent Ca²⁺ channels, which in turn results in a reduction of K⁺ efflux and in cell depolarization.

This article has been cited by other articles:

				J. S. Denton, F. V. McCann, and J. C. Leiter CO2 chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing Am J Physiol Cell Physiol, January 1, 2007; 292(1): C292 - C304. [Abstract] [Full Text] [PDF]

				M. M. Chernov, J. A. Daubenspeck, J. S. Denton, J. R. Pfeiffer, R. W. Putnam, and J. C. Leiter A computational analysis of central CO2 chemosensitivity in Helix aspersa Am J Physiol Cell Physiol, January 1, 2007; 292(1): C278 - C291. [Abstract] [Full Text] [PDF]

				S. C. Hempleman, S. X. Egan, J. Q. Pilarski, T. P. Adamson, and I. C. Solomon Calcium and avian intrapulmonary chemoreceptor response to CO2 J Appl Physiol, December 1, 2006; 101(6): 1565 - 1575. [Abstract] [Full Text] [PDF]

				N. A. Ritucci, J. S. Erlichman, J. C. Leiter, and R. W. Putnam Response of membrane potential and intracellular pH to hypercapnia in neurons and astrocytes from rat retrotrapezoid nucleus Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2005; 289(3): R851 - R861. [Abstract] [Full Text] [PDF]

				M. Wiemann, S. Frede, D. Bingmann, P. Kiwull, and H. Kiwull-Schone Sodium/Proton Exchanger 3 in the Medulla Oblongata and Set Point of Breathing Control Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 244 - 249. [Abstract] [Full Text] [PDF]

				P. G. Guyenet, R. L. Stornetta, D. A. Bayliss, and D. K. Mulkey Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors Exp Physiol, May 1, 2005; 90(3): 247 - 253. [Abstract] [Full Text] [PDF]

				R. W. Putnam, J. A. Filosa, and N. A. Ritucci Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1493 - C1526. [Abstract] [Full Text] [PDF]

				J. S. Erlichman, A. Cook, M. C. Schwab, T. W. Budd, and J. C. Leiter Heterogeneous patterns of pH regulation in glial cells in the dorsal and ventral medulla Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R289 - R302. [Abstract] [Full Text] [PDF]

				J. A. Filosa and R. W. Putnam Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels Am J Physiol Cell Physiol, January 1, 2003; 284(1): C145 - C155. [Abstract] [Full Text] [PDF]

				Z. Qu, G. Zhu, Z. Yang, N. Cui, Y. Li, S. Chanchevalap, S. Sulaiman, H. Haynie, and C. Jiang Identification of a Critical Motif Responsible for Gating of Kir2.3 Channel by Intracellular Protons J. Biol. Chem., May 14, 1999; 274(20): 13783 - 13789. [Abstract] [Full Text] [PDF]