STATE-DEPENDENT NICKEL BLOCK OF A HIGH-VOLTAGE-ACTIVATED NEURONAL CALCIUM-CHANNEL

Effects of nickel ions (Ni2+) on noninactivating calcium channels in s quid giant fiber lobe (GFL) neurons were investigated with whole cell voltage clamp. Three different effects of Ni2+ were observed to be ass ociated with distinct Ca2+ channel activation states. 1) Nickel ions a ppear to stabilize closed channel states and, as a result, slow activa tion kinetics. 2)Nickel ions block open channels with little voltage d ependence over a wide range of potentials. 3) Block of open channels b y 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 presen ce of two distinct types of Ni2+ block that we propose correspond to t wo previously identified open states of the calcium channel. These res ults, 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 GF L calcium channel complex in ways that depend on channel activation st ate.