Role of prostatic interstitial cells in prostate motility

Abstract

The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This review summarises the role of prostatic interstitial cells (PICs) in the generation of the spontaneous tone in the prostate. It presents current knowledge of the role of Ca²⁺ plays in PIC pacemaking, as well as the mechanisms by which this spontaneous activity triggers slow wave generation and stromal contraction. PICs display a small T-type Ca²⁺ current (I_CaT) and a large L-type Ca²⁺ current (I_CaL). In contrast to other interstitial cells in the urinary and gastrointestinal tracts, spontaneous Ca²⁺ signalling in PICs is uniquely dependent on Ca²⁺ influx through I_CaL channels. A model of prostatic pacemaking is presented describing how I_CaL can be triggered by an initial membrane depolarization evoked upon the selective opening of Ca²⁺-activated Cl^– channels by Ca²⁺ flowing only through I_CaT channels. The resulting current flow through I_CaL results in release of Ca²⁺ from internal stores and the summation of Cl^–-selective spontaneous transient depolarizations (STDs) to form pacemaker potentials that propagate passively into the prostatic stroma to evoke regenerative action potentials and excitation-contraction coupling.