Ion Channels and Intracellular Calcium Signalling in Corpus Cavernosum

The corpus cavernosum smooth muscle is important for both erection of the penis and for maintaining penile flaccidity. Most of the time, the smooth muscle cells are in a contracted state, which limits filling of the corpus sinuses with blood. Occasionally, however, they relax in a co-ordinated manner, allowing filling to occur. This results in an erection. When contractions of the corpus cavernosum are measured, it can be deduced that the muscle cells work together in a syncytium, for not only do they spontaneously contract in a co-ordinated manner, but they also synchronously relax. It is challenging to understand how they achieve this.In this review we will attempt to explain the activity of the corpus cavernosum, firstly by summarising current knowledge regarding the role of ion channels and how they influence tone, and secondly by presenting data on the intracellular Ca²⁺ signals that interact with the ion channels. We propose that spontaneous Ca²⁺ waves act as a primary event, driving transient depolarisation by activating Ca²⁺-activated Cl^- channels. Depolarisation then facilitates Ca²⁺ influx via L-type voltage-dependent Ca²⁺ channels. We propose that the spontaneous Ca²⁺ oscillations depend on Ca²⁺ release from both ryanodine- and inositol trisphosphate (IP₃)-sensitive stores and that modulation by signalling molecules is achieved mainly by interactions with the IP₃-sensitive mechanism. This pacemaker mechanism is inhibited by nitric oxide (acting through cyclic GMP) and enhanced by noradrenaline. By understanding these mechanisms better, it might be possible to design new treatments for erectile dysfunction.