Permeation of barium and cadmium through slowly inactivating calcium channels in cat sensory neurones.

1. Instantaneous current-voltage (I-V) relations were measured from tail currents with 10 mM-external calcium at 20 degrees C. The I-V relations had a lower potential dependence than predicted by the Goldman-Hodgkin-Katz constant-field equation. Previously proposed symmetric two-site three-barrier (2S3B) rate theory models were able to account for the I-V relations reasonably well. 2. Reversal of the current flow through the calcium channels was recorded using 10 mM-barium internally and 20 mM-barium externally. The channels appeared to rectify at positive potentials, a property not consistent with symmetric rate theory models. 3. Externally applied cadmium ions blocked the calcium channels through at least two sites. One high-affinity blocking site was located within the membrane electric field and had a dissociation constant of around 16 microM at O mV. Cadmium block at this site was relieved with hyperpolarization with a voltage dependence equivalent to a divalent cation moving through about 75% of the membrane electric field. 4. A low-affinity potential-independent blocking site also appeared to be present, having a dissociation constant of around 106 microM. 5. Cadmium had significant effects on the tail current kinetics at potentials close to 0 mV, presumably due to slow unblocking events. The rate at which cadmium ions left the calcium channel free to conduct was estimated to be about 3300 s-1 at +10 mV.