The Journal of Neurophysiology Vol. 77 No. 2 February 1997, pp. 1023-1028
Copyright ©1997 The American Physiological Society

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Ca²⁺ Channel Antagonist U-92032 Inhibits Both T-Type Ca²⁺ Channels and Na⁺ Channels in Hippocampal CA1 Pyramidal Neurons

Robert B. Avery and Daniel Johnston

Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

Avery, Robert B. and Daniel Johnston. Ca²⁺ channel antagonist U-92032 inhibits both T-type Ca²⁺ channels and Na⁺ channels in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1023-1028, 1997. The effects of 7-[[4-[bis(4-fluoropheny l ) - m e t h y l ] - 1 - p i p e r a z i n y l ] m e t h y l ] - 2 - [ ( 2 - h y d r o x y e t h y l ) a m i n o ]4 -( 1 - m e t h y l e t h y l ) - 2 , 4 , 6 - c y c l o h e p t a t r i e n - 1 - o n e   ( U - 9 2 0 3 2 ) ,   anewly described Ca²⁺ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca²⁺ currents (~20% inhibition) but not high-voltage-activated (HVA) Ca²⁺ currents. Ethanol (0.2%) did not affect Ca²⁺ currents. U-92032 selectively inhibited T-type Ca²⁺ currents (median inhibiting concentration ~ 500 nM). HVA Ca²⁺ currents were less sensitive, with ~75% of the current resistant at 10 µM. Inhibition of Ca²⁺ currents was reversible. U-92032 inhibited Na⁺ currents at concentrations similar to those required for T-type currents (>33% block at 1 µM). Block of Na⁺ currents took several minutes to develop and was irreversible. Voltage-gated K⁺ currents were insensitive to U-92032 (1 or 10 µM). These results indicate that U-92032 inhibits both T-type Ca²⁺ channels and Na⁺ channels, constraining its utility in certain studies. Among Ca²⁺ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

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