Facilitation of calcium-dependent potassium current.
The activation of Ca-dependent K+ current, Ic, was studied in macropatches on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp pulse was applied repeatedly, Ic facilitated in a manner that resembled the facilitation of synaptic transmitter release. Facilitation was characterized by an increase in Ic amplitude, a progressive increase in instantaneous outward current, and a decrease in utilization time. Experiments were done to investigate the mechanism responsible for Ic facilitation. Facilitation was reduced by microinjection of an exogenous Ca2+ buffer into the cytoplasm, indicating that facilitation is a Ca(2+)-dependent process. It was also reduced at elevated temperatures. Conversely, facilitation was greatly potentiated by blocking the Na/Ca exchange mechanism. It is concluded that the facilitation of Ca-dependent K+ current results from the accumulation of Ca2+ at the inner face of the membrane during the repeated activation of Ca2+ channels by depolarization. The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to measure changes in [Ca]i near the cell membrane during repeated depolarizing pulses and the interpretation of these results was aided by numerical simulations of Ca2+ accumulation, diffusion, and buffering in the peripheral cytoplasm. These experiments showed that the time course of Ic facilitation matches the time course of Ca2+ accumulation at the membrane. It was found that the strength of Ic facilitation varies among patches on the same neuron, suggesting that the accumulation of Ca2+ is not uniform along the inner surface of the membrane and that gradients in [Ca]i develop and are maintained during trains of depolarizing pulses. Potential mechanisms that may lead to local differences in Ca2+ accumulation and Ic facilitation are discussed.
Thompson
S H
SH
Department of Biological Sciences, Stanford University, Pacific Grove, California 93950.
D000814:Aniline Compounds; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D003198:Computer Simulation; D004553:Electric Conductivity; D005456:Fluorescent Dyes; D008959:Models, Neurological; D008974:Mollusca; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D019831:Sodium-Calcium Exchanger; D013696:Temperature; D014966:Xanthenes
D000814:Aniline Compounds; D002021:Buffers; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D014966:Xanthenes; C059715:Fluo-3; D011188:Potassium; D002118:Calcium