K+ channel modulation of slow wave activity in the guinea-pig prostate.
OBJECTIVE
The aim of this study was to investigate the role of different K(+) channel populations and the inhibitory effect of various exogenously applied K(+) channel openers in the regulation of slow wave activity in the guinea-pig prostate.


METHODS
Recordings of membrane potential were made using intracellular microelectrodes.


RESULTS
Tetraethylammonium (TEA 300 micro M and 1 mM), iberiotoxin (150 nM) and 4-aminopyridine (4-AP 1 mM) increased the frequency of slow wave discharge. Apamin (1-200 nM) and glibenclamide (1 micro M) had no effect on slow wave activity. Lemakalim (1 micro M) and PCO-400 (1 micro M) abolished the slow waves, as did sodium nitroprusside (SNP 10 micro M) and calcitonin gene-related peptide (CGRP 100 nM). The inhibitory effect of these agents was independent of a significant change in membrane potential. In the presence of 4-AP (1 mM), TEA (1 mM) or glibenclamide (1 micro M) the inhibitory actions of SNP (10 micro M) were attenuated. The inhibitory actions of CGRP (100 nM) were also reversed by glibenclamide (1 micro M). In contrast, isoprenaline (1 micro M) did not alter the frequency of slow wave discharge.


CONCLUSIONS
These results demonstrate that BK(Ca) and 4-AP-sensitive K(+) channels regulate the frequency of prostatic slow wave discharge. SNP and CGRP abolish slow waves in a hyperpolarisation-independent manner, partially via opening of K(ATP) channels. BK(Ca) and 4-AP-sensitive K(+) channels also play an important role in the SNP-induced inhibition of slow wave activity. The lack of membrane hyperpolarisation associated with the SNP- and CGRP-induced inhibition implies that the channels involved in this action are not predominantly located on the smooth muscle cells.
Nguyen
D-T T
DT
Department of Pharmaceutical Biology and Pharmacology, Prostate Research Co-operative, Victorian College of Pharmacy, Monash University, Parkville Victoria, Australia.
Lang
R J
RJ
Exintaris
B
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000008:administration & dosage / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D011467:Prostate / Q000378:metabolism* / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D019789:Tetraethylammonium / Q000008:administration & dosage / Q000494:pharmacology
D001578:Benzopyrans; D003517:Cyclopentanes; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; C073091:SDZ PCO 400; D009599:Nitroprusside; D001030:Apamin; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol; D005905:Glyburide