Human sperm are endowed with voltage-dependent calcium channels (VDCC) that produce increases in [Ca2+](i) in response to depolarization with KCl. These channels are stimulated during "capacitation", a complex biochemical process, accompanied by a slight pHi alkalization, that sperm must accomplish to acquire the ability to fertilize the egg. The stimulation can be explained in part by the fact that in non-capacitated sperm, calcium influx through VDCC is stimulated by pHr alkalization in the range of pHi observed during capacitation. In this work, we explored the effect of pHi oil VDCC in capacitated sperm loaded with fura ff. Strikingly, the pHi sensitivity of VDCC increased similar to 7-fold when sperm was capacitated, as compared with non-capacitated sperm. This finding suggests that the pHi sensitivity of VDCC call be modulated during capacitation so that a combined effect of pHi alkalization and biochemical regulation enhances calcium influx through these channels. (c) 2006 Elsevier Inc. All rights reserved.