Neuronal voltage gated potassium channels modulate nitric oxide synthesis in rabbit corpus cavernosum

FM Sharabi, AM Senbel, HM Abdel Moneim, MM Mohy El-Din. Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt

Potassium channels (K+ Ch) in corpus cavernous play an important role in the regulation of penile erection.

Nitric oxide (NO) acts through opening of K+ Ch leading to hyperpolarization and relaxation (1). This study aims to assess the role of the different K+ Ch in NO action/synthesis/release in the corpus cavernosum.

Tension studies using isolated rabbit corpus cavernosum strips were conducted (2). Results are expressed as mean ± SEM of 6-8 experiments.

Electric field stimulation (EFS, 2-16 Hz) evoked frequency-dependent relaxations of the PE (phenylephrine)-precontracted strips. Both TEA (tetraethylammonium) (10-3M) (non-selective K+ Ch blocker) and 4-aminopyridine (10-3M) (voltage-gated K+ Ch blocker) significantly potentiated the responses to EFS by 153.30±18.43% and 74.86±6.46% respectively at 2 Hz. This potentiatory effect was abolished in presence of NG-nitro-L-arginine (non-selective nitric oxide synthase inhibitor)(10-5M).

Both glibenclamide(10-5M) (ATP- sensitive K+ Ch blocker) and TEA (10-5M) (large conductance calcium-activated K+ Ch blocker) failed to modify the responses to EFS. On other hand, TEA (10-3M), 4-aminopyridine (10-3M) and TEA (10-5M), but not glibenclamide (10-5M), significantly reduced the responses to SNP (sodium nitroprusside) (10-8-10-4M). Relaxation induced by SNP (10-6M) was reduced from 63.9±3.51% to 38.39±4.4%, 49.28±4.52% and 47.77±4.65% in presence of TEA (10-3M), 4-aminopyridine (10-3M) and TEA (10-5M) respectively.

In summary, NO relaxes rabbit corpus cavernosum via activating different types of K+ Ch of which the ATP sensitive K+ Ch appears to be of no importance. This study provides preliminary evidence for the presence of prejunctional voltage gated K+ Ch the blockade of which may increase the neuronal synthesis of NO. Further studies using specific blockers of NO synthesis are recommended.

(1) Christ GJ (2002). J Androl 14: 319-328

(2) Sparwasser C et al. (1994). J Urol 152: 2159-2163