Penile erection is dependent on the nitric oxide (NO)/cGMP‐dependent protein kinase I (PKGI) pathway. One important target of PKGI in smooth muscle is the large‐conductance, calcium‐activated potassium (BK) channel, which upon activation hyperpolarizes the smooth muscle cell membrane, causing relaxation. Relaxation of arterial and corpus cavernosum smooth muscle (CCSM) is necessary to increase blood flow into the corpora cavernosa that leads to penile tumescence. We investigated the functional role of BK channels in the corpus cavernosum utilizing a knock‐out mouse lacking the Slo gene (Slo^−/−) responsible for the pore‐forming subunit of the BK channel. Whole‐cell currents were recorded from isolated CCSM cells of Slo^+/+ and Slo^−/− mice. Iberiotoxin‐sensitive voltage‐ and [Ca²⁺]‐activated K⁺ currents, the latter activated by local transient calcium releases (calcium sparks), were present in Slo^+/+ CCSM cells, but absent in Slo^−/− cells. CCSM strips from Slo^−/− mice demonstrated a four‐fold increase in phasic contractions, in the presence of phenylephrine. Nerve‐evoked relaxations of precontracted strips were reduced by 50%, both in strips from Slo^−/− mice and by blocking BK channels with iberiotoxin in the Slo^+/+ strips. Consistent with the in vitro results, in vivo intracavernous pressure exhibited pronounced oscillations in Slo^−/− mice, but not in Slo^+/+ mice. Furthermore, intracavernous pressure increases to nerve stimulation, in vivo, were reduced by 22% in Slo^−/−mice. These results indicate that the BK channel has an important role in erectile function, and loss of the BK channel leads to erectile dysfunction.

The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5 H)-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D₂-methoxime expression in the bladder was significantly ( P ≤ 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E₂was significantly ( P ≤ 0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis.

Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments.