Pflugers Arch - Eur J Physiol (2003) 446:88–99 DOI 10.1007/s00424-002-0995-6 ION CHANNELS, TRANSPORTERS Jun Hee Kim · Sun Young Shin · Sang Soon Yun · Tae Jin Kim · Seung-June Oh · Kwang Myung Kim · Young-Shin Chung · Eun-Kyoung Hong · Dae-Yong Uhm · Sung Joon Kim Voltage-dependent ion channel currents in putative neuroendocrine cells dissociated from the ventral prostate of rat Received: 20 September 2002 / Accepted: 20 November 2002 / Published online: 21 February 2003  Springer-Verlag 2003 Abstract Prostate neuroendocrine (NE) cells play im- portant roles in the growth and differentiation of the prostate. Following enzymatic digestion of rat ventral prostate, the whole-cell patch-clamp technique was applied to dark, round cells that exhibited chromogra- nin-A immunoreactivity, a representative marker of NE cells. Under zero current-clamp conditions, putative NE cells showed hyperpolarized resting membrane potentials of some 70 mV, and spontaneous action potentials were induced by an increase in external [K + ] or by the injection of current. Using a CsCl pipette solution, step-like depolarization activated high-voltage-activated Ca 2+ cur- rent (HVA I Ca ) and tetrodotoxin-resistant voltage-activat- ed Na + current. The HVA I Ca was blocked by nifedipine and w-conotoxin GVIA, L-type and N-type Ca 2+ channel blockers, respectively. Using a KCl pipette solution, the transient outward K + current (I to ), Ca 2+ -activated K + currents (I K,Ca ), the non-inactivating outward current and an inwardly rectifying K + current (I Kir ) were identi- fied. I K,Ca was suppressed by charybdotoxin (50 nM), iberiotoxin (10 nM) or clotrimazol (1 mM), but not by apamine (100 nM). I to was inhibited by 4-aminopyridine (5 mM). I Kir was identified as a Ba 2+ -sensitive inwardly rectifying current in the presence of a high-K + bath solution. The voltage- and Ca 2+ -activated ion channels could play significant roles in the regulation of neuro- hormonal secretion in the prostate. Keywords Ion channel · Neuroendocrine cell · Prostate · Rat · TTX-resistant sodium channel Introduction The human prostate is the largest sex accessory gland of males and the site where the largest number of urological problems can arise, including benign prostate hyperplasia (BPH) or prostate cancer. Given these clinical implica- tions, knowledge about the normal physiology of the prostate gland is essential. The prostate gland consists of a complex ductal system lined with exocrine epithelial cells, neuroendocrine (NE) cells and basal stem cells embedded in a stromal matrix [17]. Prostate NE cells with paracrine/autocrine properties may regulate the growth, as well as the function, of surrounding cells and the stromal matrix [3, 5, 6, 8]. From immunohistochemical studies, NE cells of the prostate are believed to secrete a variety of neurosecretory products such as serotonin, histamine, calcitonin and parathyroid hormone-related peptides [19, 30]. Like other NE cells, prostate NE cells can be identified by chromogranin-A immunoreactivity. The density of chromogranin-A positive cells is reportedly higher in the neoplastic region of prostate hyperplasia than in the normal prostate [11]. Focal neuroendocrine differentiation occurs in prostatic adenocarcinomas and those tumors with extensive and multifocal neuroendocrine differenti- ation tend to be more aggressive and resistant to hormonal therapy, providing a prognostic marker of the prostate cancer [5]. Given their physiological and pathophysio- logical importance, knowledge of ion channels in prostate NE cells is needed in an effort to understand their functional significance. We recently isolated single prostate cells by employing enzymatic digestion of the ventral lobe of rat prostate. J. H. Kim · S. Y. Shin · D.-Y. Uhm · S. J. Kim ( ) ) Department of Physiology Sungkyunkwan University School of Medicine, 440-746 Suwon, Korea e-mail: sjoonkim@med.skku.ac.kr Tel.: +82-31-2996104 Fax: +82-31-2996129 S. S. Yun · T. J. Kim Department of Pathology, Sungkyunkwan University School of Medicine, 440-746, Suwon, Korea S.-J. Oh · K. M. Kim Department of Urology, Seoul National University Medical College, 110-790 Seoul, Korea Y.-S. Chung · E.-K. Hong Medvill Central Research Laboratory, Pyungchang-Dong 432-10, Seoul, Korea