Transient increases in extracellular K+ produce two pharmacological distinct cytosolic Ca2+ transients.
Transient increases in extracellular K+ are observed under various conditions, including repetitive neuronal firing, anoxia, ischemia and hypoglycemic coma. We studied changes in cytoplasmic Ca2+ ([Ca2+]cyt) evoked by pulses of KCl in human neuroblastoma SH-SY5Y cells and rat dorsal root ganglia (DRG) neurons at 37 degrees C. A "pulse" of KCl evoked two transient increases in [Ca2+]cyt, one upon addition of KCl (K+on) and the other upon removal of KCl (K+off). The K+on transient has been described in many cell types and is initiated by the activation of voltage-dependent Ca2+ channels followed by Ca2+-evoked Ca2+ release from intracellular Ca2+ stores. The level of KCl necessary to evoke the K+off transient depends on the type of neuron, in SH-SY5Y cells it required 100 mM KCl, in most (but not all) of dorsal root ganglia neurons it could be detected with 100-200 mM KCl and in a very few dorsal root ganglia neurons it was detectable at 20-50 mM KCl. In SH-SY5Y cells, reduction of extracellular Ca2+ inhibited the K+on more strongly than the K+off and slowed the decay of K+off. Isoflurane (1 mM) reduced the K+on)- but not the K+off-peak. However, isoflurane slowed the decay of K+off. The nonspecific cationic channel blocker La3+ (100 microM) had an effect similar to that of isoflurane. Treatment with thapsigargin (TG) at a concentration known to only deplete IP3-sensitive Ca2+ stores did not affect K+on or K+off, suggesting that Ca2+ release from the IP3-sensitive Ca2+ stores does not contribute to K+on and K+off transients and that the thapsigargin-sensitive Ca2+ ATPases do not contribute significantly to the rise or decay rates of these transients. These findings indicate that a pulse of extracellular K+ produces two distinct transient increases in [Ca2+]cyt.
Corrales
Alexandra
A
Anesthesiology Department, New York University School of Medicine, 550 First Avenue, RR605, New York, NY 10016, USA.
Montoya G
José V
JV
Sutachan
Jhon-Jairo
JJ
Cornillez-Ty
Genoveve
G
Garavito-Aguilar
Zayra
Z
Xu
Fang
F
Blanck
Thomas J J
TJ
Recio-Pinto
Esperanza
E
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D011188:Potassium; D002118:Calcium