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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Stereoselectivity of Ca2+ channel block by dihydropyridines: no modulation by the voltage protocol.

The L-type Ca2+ current inhibition by the enantiomers of the dihydropyridine niguldipine was investigated at various holding potentials (-40 to -120 mV) and stimulus frequencies (0.1-1 Hz), using guinea-pig ventricular myocytes. Block of whole-cell current is both voltage- and concentration-dependent. (S)-Niguldipine is more potent than its (R)-enantiomer. However, the extent of enantioselectivity is rather small (< or = x 4.4). Importantly, this value does not increase when stimulus conditions favour the inactivated channel state, although this leads to more potent block. This is in contrast to our expectation based on modulated receptor hypothesis, and to the high enantioselectivity of niguldipine binding found in guinea-pig heart membranes (x 40). We conclude that the common modulated receptor hypothesis had to be refined to explain the effects of niguldipine enantiomers.[1]


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