Non-genomic action of ovarian steroid hormones on a transient voltage-dependent K+ current in human luteinised granulosa cells

Abstract

Non-genomic effects of steroids mediating fast cellular actions have been intensively studied in the brain and in the cardiovascular system, where ion channels were identified as one of the targets. Although steroid concentrations in the ovary exceed by orders of magnitude those in brain and heart, the potential interactions of steroids and ion channels in endocrine cells of this organ are unknown; partially, because of only rudimentary knowledge of molecular identity and function of ovarian ion channels. Here we provide novel evidence for a K+ channel in the human ovary, which is inhibited by sex steroid hormones. Using an electrophysiological approach, we characterised a fast activating and inactivating K+ current (IA) in cultured human granulosa cells (GCs). Within seconds, IA was partially inhibited by the major ovarian steroids (progesterone, 17β-estradiol, testosterone) at physiologically relevant concentrations (1µM). Phrixotoxin-2 (PaTx-2) partially blocked IA indicating a contribution of voltage-dependent K+ (Kv) channels of the Kv4 class (Kv4.2 and/or Kv4.3). Moreover, the steroids did not exhibit any effect on IA when Kv4 channels had been blocked by PaTx-2. RT-PCR and cDNA array analysis demonstrated the presence of mRNA for Kv4.2, but not for Kv4.3 in cultured human GCs and in the human ovary. In addition, Kv4.2 channel protein was detected by immunohistochemistry in human follicular and luteal granulosa cells emphasising its physiological relevance. Based on our functional and molecular data we identified Kv4.2 as the channel underlying the steroid-sensitive fraction of IA and we, therefore, propose a role of this K+ channel as ovarian steroid sensor.