‘Effects of aging on the spontaneous activity in the guinea pig prostate gland’
thesisposted on 02.02.2017, 02:47 by Dey, Anupama
Spontaneous contractile as well as electrical activity was recorded from intact preparations of guinea pig prostate. Electrical recordings from the smooth muscle stroma identified the presence of 4 different types of activity; STDs, pacemaker potentials, slow wave activity as well as spike potential activity. The proportions of the respective waveforms, however appeared to change with age suggesting a change in the intercellular communication/and or ion channel populations with age. A change in the proportions of the various cell types was excluded based on previous immuno-histochemical findings (Kusljic 2007). Specifically, it was demonstrated that with an increase in age there appeared to be a decrease in the prevalence of slow wave activity, an increase in spike potential activity and an absence of pacemaker potential recordings. In the young guinea pig prostate,approximately 10% of all recordings were pacemaker potentials (Exintaris et al., 2002), thought to originate from the summation of STD units, which are likely to be dependent on the opening of Ca2+ activated Cl- channels (Lang et al., 2004). These events are thought to arise from the PIC c-kit positive cell layer between the smooth muscle and glandular component of the guinea pig prostate (Exintaris et al., 2002; Kusljic 2007). In addition, the spontaneous contractile activity recorded within both age groups of guinea pigs indicated an increased basal level of smooth muscle tone with the aging animals, although amplitude of these contractions was not altered across both age groups. The application of various gap junctional inhibitors specific for CX43 caused cessation of electrical activity among both age groups of guinea pig prostate. In addition, the application of a two concentrations of the same gap junction uncouplers on the spontaneous contractile activity also inhibited contractions on both age groups at the higher concentration, although only abolished contractions in the aging prostates at the lower concentration. Previous studies have reported an increase in the expression of CX43 in human BPH specimens (Habermann et al., 2001) which may account for the sensitivity to the aging prostate of the lower concentrations of gap junction inhibitors. Altogether, these results suggest that CX43 is crucial in the transmission of electrical signals as well as coordination of contraction of smooth muscle. In BPH it is established that an increase in smooth muscle tone of the prostate may be attributed to a reduction in the NO mediated relaxation of the smooth muscle (Aikawa et al., 2001). It was established that application of the NOS inhibitor L-NAME increased the frequency of spontaneous activity in the younger animals more significantly than the aging guinea pigs. In addition, ODQ significantly increased activity in the young model although had no effect on the frequency of spontaneous activity in the aging guinea pig it is established that an increase in smooth muscle tone of the prostate may be attributed to a reduction in the NO mediated relaxation of the smooth muscle (Aikawa et al., 2001). It was established that application of the NOS inhibitor L-NAME increased the frequency of spontaneous activity in the younger animals more significantly than the aging guinea pigs. In addition, ODQ significantly increased activity in the young model although had no effect on the frequency of spontaneous activity in the aging guinea pig prostate. Treatment with the addition of NO directly however, abolished contractions across both age groups of prostate. Results suggest that there is a reduction in the basal levels of NO in the aging prostates, rather than a change in the post receptor mechanisms themselves. In summary, the results presented within this thesis indicate that there is a change in the proportion of electrical activities displayed with an increase in age in the guinea pig prostate. Furthermore, an increase in the basal tension of aging prostate preparations as well as a decrease in basal NO levels, is also indicative of an increase in smooth muscle tone with age which can be correlated with the changes that occur with age and/or BPH. Increase in the knowledge of the changes in spontaneous electrical and contractile activities that occur with respect to age and disease state, may be of significant clinical importance in providing more specific drug targets for this condition.