|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 98, 751-770, Copyright © 1991 by The Rockefeller University Press
ARTICLES |
RH Chow
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
The mechanism of Cd2+ block of Ca2+ currents (ICa) was explored in squid neurons using whole-cell patch clamp. Control currents activated sigmoidally, more rapidly at more positive potentials, and did not inactivate significantly. External Cd2+ up to 250 microM reduced ICa reversibly. For small depolarizations, the current for a step of 10 ms increased to a maintained value, resembling the control; but for Vm greater than 0 mV, the increase was followed by a decrease, as Cd2+ block became greater. Final block was greater for larger depolarizations. At 0 mV the half-blocking concentration was 125 microM. Tail currents, measured as channels close, had an initial "hook" when recorded in Cd2+: currents increased transiently, then decreased. This suggests that Cd2+ escapes from some channels, which then conduct briefly before closing. Analysis of tail currents shows that Cd2+ does not slow channel closing. The data can be explained if Cd2+ is a permeant blocker of Ca2+ channels and if channels can close when occupied by Cd2+. Cd2+ permeates the channels, but binds transiently to a site in the pore, obstructing the passage of other ions (e.g., Ca2+). Dwell time depends on the transmembrane potential, becoming shorter for more negative internal potentials. A five-state model was used to simulate the steady-state and kinetic features. It combines a Hodgkin-Huxley type m2 gating scheme and a one-site Woodhull ionic blockage model for a permeant blocker and includes a closed blocked state. To fit the data, the binding site for Cd2+ had to be near the outer end of the pore, with a well depth of -12.2 RT, and with a barrier at each end of the pore. The model predicts that the Cd2+ entry rate is nearly voltage independent, but the exit rate is steeply voltage dependent (e-fold/17 mV). Analysis further suggests that the channel closes at a normal rate with Cd2+ in the pore.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H.-P. Huang, S.-R. Wang, W. Yao, C. Zhang, Y. Zhou, X.-W. Chen, B. Zhang, W. Xiong, L.-Y. Wang, L.-H. Zheng, et al. Long latency of evoked quantal transmitter release from somata of locus coeruleus neurons in rat pontine slices PNAS, January 23, 2007; 104(4): 1401 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Marcotti, S. M. van Netten, and C. J. Kros The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano -electrical transducer channels J. Physiol., September 1, 2005; 567(2): 505 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Pennec, H. Talarmin, M. Droguet, M.-A. Giroux-Metges, M. Gioux, and G. Dorange Characterization of the voltage-activated currents in cultured atrial myocytes isolated from the heart of the common oyster Crassostrea gigas J. Exp. Biol., October 15, 2004; 207(22): 3935 - 3944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Day, P. A. Olson, J. Platzer, J. Striessnig, and D. J. Surmeier Stimulation of 5-HT2 Receptors in Prefrontal Pyramidal Neurons Inhibits Cav1.2 L-Type Ca2+ Currents Via a PLCbeta /IP3/Calcineurin Signaling Cascade J Neurophysiol, May 1, 2002; 87(5): 2490 - 2504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mitra and M. M. Slaughter Calcium-induced Transitions between the Spontaneous Miniature Outward and the Transient Outward Currents in Retinal Amacrine Cells J. Gen. Physiol., April 2, 2002; 119(4): 373 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. McFarlane and W. F. Gilly State-Dependent Nickel Block of a High-Voltage-Activated Neuronal Calcium Channel J Neurophysiol, October 1, 1998; 80(4): 1678 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wakamori, M. Strobeck, T. Niidome, T. Teramoto, K. Imoto, and Y. Mori Functional Characterization of Ion Permeation Pathway in the N-Type Ca2+ Channel J Neurophysiol, February 1, 1998; 79(2): 622 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bernal, J.-H. Lee, L. L. Cribbs, and E. Perez-Reyes Full Reversal of Pb++ Block of L-Type Ca++ Channels Requires Treatment with Heavy Metal Antidotes J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 172 - 180. [Abstract] [Full Text]
|
|
|
|
|
|
P. Mitra and M. M. Slaughter Calcium-induced Transitions between the Spontaneous Miniature Outward and the Transient Outward Currents in Retinal Amacrine Cells J. Gen. Physiol., April 2, 2002; 119(4): 373 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Contreras, W. Nonner, and E. N. Yamoah Ca2+ transport properties and determinants of anomalous mole fraction effects of single voltage-gated Ca2+ channels in hair cells from bullfrog saccule J. Physiol., February 1, 2002; 538(3): 729 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
