Anupa Dey

Spontaneous electrical activity in the prostate gland.

The cellular mechanisms that underlie the initiation, maintenance and propagation of electrical activity in the prostate gland remain little understood. Intracellular microelectrode recordings have identified at least two distinct electrical waveforms: pacemaker potentials and slow wave activity. By analogy with the intestine, we have proposed that pacemaker activity arises from a morphologically distinct group of c-Kit positive interstitial cells that lie mainly between the glandular epithelium and smooth muscle layers. We speculate that pacemaker activity arising from the prostatic interstitial cells (PICs) is likely to propagate and initiate slow wave activity in the smooth muscle cells resulting in contraction of the stromal smooth muscle wall. While spontaneous electrical activity in the prostate gland is myogenic in origin, it is clear that nerve-mediated agents are able to modulate this activity. Excitatory agents such as histamine, phenylephrine and a raised potassium saline all increase slow wave discharge. In contrast, nitric oxide donors reduce or abolish the spontaneous electrical events. However, the cellular mechanisms underlying the action of various endogenously released agents remain to be elucidated.

Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland

BACKGROUND AND PURPOSE To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs.

Nitric Oxide Signaling Pathways Involved in the Inhibition of Spontaneous Activity in the Guinea Pig Prostate

PURPOSE We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. MATERIALS AND METHODS Conventional intracellular microelectrode and tension recording techniques were used. RESULTS The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p<0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p<0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p<0.05). CONCLUSIONS The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.

Spontaneous Electrical Waveforms in Aging Guinea Pig Prostates

PURPOSE We characterized spontaneous electrical activity in the aging guinea pig prostate. MATERIALS AND METHODS Membrane potential recordings were made using conventional single microelectrode recording techniques. RESULTS Three types of spontaneous waveforms were recorded, including spikes, slow waves and spontaneous transient depolarizations. Spikes were classified as hyperactive or active. Active cells showed a mean +/- SEM frequency of 5.06 +/- 0.63 minutes(-1), significantly different from that in hyperactive cells (362.05 +/- 151.82 minutes(-1), p <0.05). After hyperpolarization amplitude was also significantly different in the active and hyperactive groups (17.80 +/- 1.98 vs 9.96 +/- 1.05 mV). Spike activity was abolished by 1 microM nifedipine in 7 preparations (p <0.05). Slow wave activity occurred at a frequency of 5.2 +/- 0.5 minutes(-1). The spike component of slow wave activity was abolished by 1 microM nifedipine, although the depolarizing transient remained unaltered from control values (8.1 +/- 3.1 mV, paired Students t test p >0.05). Spontaneous transient depolarizations were recorded in the presence of slow waves in 10 preparations and of spikes in 13, and in quiescent cells in 9. Spontaneous transient depolarization frequency was highest in otherwise quiescent cells (24.55 +/- 6.48 minutes(-1)) compared to that in the presence of slow waves or spikes. Adding 1 microM nifedipine in 5 preparations did not significantly affect any measured parameters (p >0.05). Pacemaker potentials were not recorded in the aging prostate. CONCLUSIONS With increased age there is an increase in spike activity, which could conceivably explain the increased prostatic tone that accompanies aging. Spike activity and the spike component of the slow wave were abolished by nifedipine, suggesting a role for L-type channels. Finally, spontaneous transient depolarizations were unaffected by nifedipine, suggesting that mechanisms other than Ca(2+) entry via L-type channels are responsible for their generation and maintenance.

Prostatic Interstitial Cells in Ageing Guinea Pig Prostates

Objective: Prostatic interstitial cells (PIC) have been previously identified in the young guinea pig and human prostates and have been suggested to be a potential new therapeutic target for diseases of the prostate gland. In this study we have established the presence of PIC and their intercellular communication via connexin 43, in the ageing guinea pig prostate. Materials and Methods: Immunohistochemical and electrophysiological techniques were used. Results: Microscopic examination of preparations of guinea pig pros-tate revealed the presence of c-Kit immunoreactive cells in the region between the smooth muscle (SM) and glandular layers in ageing guinea pigs. Connexin 43 immunoreactive cells were observed within the border between the glandu-lar layer and SM layer but not within SM layer itself. Three distinct types of electrical activity were recorded in the ageing guinea pig prostate gland: slow waves, spontaneous transient depolarisations and spike potentials. Pacemaker potentials were not recorded. Conclusion: C-Kit immuno-reactive cells are present in the ageing guinea pig prostate gland and appear to communicate to each other, but not to SM cells via connexin 43 protein. Ageing prostates do not appear to exhibit pacemaker activity, although PIC are pres-ent, indicating that the characteristics of the PIC may change with age. These results have implications in better under-standing and treating prostate-specific conditions such as benign prostatic hyperplasia.

Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland

To examine the effects of the α1A‐adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea‐pig prostate gland.

Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions.