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J Neurophysiol 80: 1678-1685, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 80 No. 4 October 1998, pp. 1678-1685
Copyright ©1998 The American Physiological Society

State-Dependent Nickel Block of a High-Voltage-Activated Neuronal Calcium Channel

Matthew B. McFarlane1, 2 and William F. Gilly2

1 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford 94305; and 2 Department of Biological Sciences, Hopkins Marine Station, Stanford University, Pacific Grove, California 93950

McFarlane, Matthew B. and William F. Gilly. State-dependent nickel block of a high-voltage-activated neuronal calcium channel. J. Neurophysiol. 80: 1678-1685, 1998. Effects of nickel ions (Ni2+) on noninactivating calcium channels in squid giant fiber lobe (GFL) neurons were investigated with whole cell voltage clamp. Three different effects of Ni2+ were observed to be associated with distinct Ca2+ channel activation states. 1) Nickel ions appear to stabilize closed channel states and, as a result, slow activation kinetics. 2) Nickel ions block open channels with little voltage dependence over a wide range of potentials. 3) Block of open channels by Ni2+ becomes more effective during an extended strong depolarization, and this effect is voltage dependent. Recovery from this additional inhibition occurs at intermediate voltages, consistent with the presence of two distinct types of Ni2+ block that we propose correspond to two previously identified open states of the calcium channel. These results, taken together with earlier evidence of state-dependent block by omega -agatoxin IVA, suggest that Ni2+ generates these unique effects in part by interacting differently with the external surface of the GFL calcium channel complex in ways that depend on channel activation state.




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