P‐type calcium channels in rat neocortical neurones.

1. The high threshold, voltage‐activated (HVA) calcium current was recorded from acutely isolated rat neocortical pyramidal neurones using the whole‐cell patch technique to examine the effect of agents that block P‐type calcium channels and to compare their effects to those of omega‐conotoxin GVIA (omega‐CgTX) and nifedipine. 2. When applied at a saturating concentration (100 nM) the peptide toxins omega‐Aga‐IVA and synthetic omega‐Aga‐IVA blocked 31.5 and 33.0% of the HVA current respectively. 3. A saturating concentration of nifedipine (10 microM) inhibited 48.2% of the omega‐Aga‐IVA‐sensitive current, whereas saturating concentrations of both omega‐Aga‐IVA (100 nM) and omega‐CgTX (10 microM) blocked separate specific components of the HVA current. 4. Partially purified funnel web spider toxin (FTX) at a dilution of 1:1000 blocked 81.4% of the HVA current and occluded the inhibitory effect of omega‐Aga‐IVA. Synthetic FTX 3.3 arginine polyamine (sFTX) at a concentration of 1 mM blocked 61.2% of the HVA current rapidly and reversibly. The effects of sFTX were partially occluded by pre‐application of omega‐Aga‐IVA. We conclude that neither FTX nor sFTX blocked a specific component of the HVA current in these cells. 5. In view of the specificity of omega‐Aga‐IVA for P‐type calcium channels in other preparations and for a specific component of the HVA current in dissociated neocortical neurones we conclude that about 30% of the HVA current in these neurones flow through P‐channels.

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