L-Type Ca2+ channels mediate the slow Ca2+-dependent afterhyperpolarization current in rat CA3 pyramidal cells in vitro.
Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal organotypic slice cultures, and the slow Ca2+-dependent K+ current or afterhyperpolarization current (IAHP) was elicited with brief depolarizing voltage jumps. The slow IAHP was suppressed by the selective L-type Ca2+ channel antagonists isradipine (2 microM) or nifedipine (10 microM). In contrast, neither omega-conotoxin MVIIA (1 microM) nor omega-agatoxin IVA (200 nM), N-type and P/Q-type Ca2+ channel antagonists, respectively, attenuated this slow outward current. The slow IAHP was significantly reduced by thapsigargin (10 microM), a Ca2+ ATPase inhibitor that depletes intracellular Ca2+ stores, and by ryanodine (10-100 microM), which blocks Ca2+-induced Ca2+ release from intracellular compartments. At this concentration thapsigargin did not modify high-threshold Ca2+ current, which was, however, blocked by isradipine. Thus, in hippocampal CA3 pyramidal cells, Ca2+ influx through L-type Ca2+ channels is necessary to trigger the slow IAHP. Furthermore, intracellular Ca2+-activated Ca2+ stores represent a critical component in the transduction pathway leading to the generation of the slow IAHP.
Tanabe
M
M
Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.
Gähwiler
B H
BH
Gerber
U
U
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D046508:Culture Techniques; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002118:Calcium