Fig. 5. Selective block of N-type Ca²⁺ channels prolonged action potential duration. (Ai) Example action potentials showing action potential broadening and block of the fast afterhyperpolarisation (fAHP) by application of the BK channel blocker iberiotoxin (IbTx, 100 nM). All spike traces refer to the first spike of the train. Inset shows an action potential train of five spikes in a CA1 pyramidal neuron from a hippocampal slice evoked by a 200 msecond depolarising current injection. ^* indicates the fAHP. (Aii) Normalised pooled data showing the slowing of action potential duration during a train of action potentials resulting from BK channel inactivation (open bars, see text). Shaded bars show that the slowing of action potential duration by IbTx (100 nM) is observed throughout the train, with the effect being sustained after the second action potential (n=6 cells, 10 spikes per cell, this and subsequent pooled data plots; ^*P<0.05). (Aiii) Example action potentials illustrating the slowing of action potential repolarisation and block of the fAHP after addition of the BK channel blocker charybdotoxin (ChTx, 10 nM). (Aiv) Normalised pooled data showing that the prolongation of action potential duration by ChTx was sustained throughout the train (n=3 cells, 10 spikes per cell). (Bi) Block of N-type Ca²⁺ channels by -conotoxin GVIA (-Ctx GVIA, 300 nM) slowed the lower half of action potential repolarisation and abolished the fAHP. (Bii) The normalised pooled data showed that -Conotoxin GVIA (300 nM) significantly slowed spike repolarisation of the first and subsequent spikes in a train (n=7 cells, 10 spikes per cell). Inset shows P/4 leak-subtracted whole-cell currents evoked by a 300 msecond depolarising voltage step to 0 mV from a holding potential of –70 mV. Evoked current was greatly reduced by application of isradipine (5 µM), indicating that L-type Ca²⁺ channels carried the majority of inward current. (Ci) Example action potentials showing that selective block of L-type Ca²⁺ channels by the dihydropyridine antagonist isradipine (10 µM) had no effect on action potential duration. (Cii) The lack of an effect for all action potentials within the train is shown in the normalised pooled data (n=9 cells, 10 spikes per cell).