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Features of L-type Ca2+ channel blockade produced by dihydropyridines (e.g. nifedipine):
The dihydropyridines gain access to their receptor irrespective of whether the channel is open or closed. However, binding of the dihydropyridines to their receptor depends on the operational mode of the channel. The L-type Ca2+ channel can switch randomly between three different modes of operation.
Click to see the three modes:
In mode 0 the channel does not open in response to depolarisation. In mode 1 channel openings caused by depolarisation are of brief duration. In mode 2 channel openings of greater duration occur. The dihydropyridines bind to the L-type channel in its mode 0 state - a state that occurs <1% of the time. Since binding affinity is increased by depolarisation, dihydropyridine blockade of the L-type channel is strongly voltage dependent.
