Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

1 Intracellular microelectrode recordings were made from circular smooth muscle of rabbit urethra. 2 The smooth muscle of urethra was spontaneously active exhibiting large, regularly occurring depolarizations, termed slow waves (SWs), 1-3 s in duration, up to 40 mV in amplitude and generated every 3-15 s and small irregularly occurring events (or summations there of) termed spontaneous transient depolarizations (STDs) of <1 s in duration. 3 The SWs and STDs were not sensitive to 10(-6) M atropine, 10(-6) M phentolamine, 10(-5) M guanethidine or 10(-6) M tetrodotoxin, indicating that they were myogenic in origin. 4 Application of 3 x 10(-6) M nifedipine or 5 x 10(-5) M GdCl3 did not inhibit the generation of SWs or STDs, indicating that activation of L-type Ca2+ channels and non-selective cation channels are not essential for their generation. However, the duration of SWs but not STDs was reduced by nifedipine, indicating L-type Ca2+ channels contribute to the plateau-like potential of SWs. 5 Application of low chloride solution (6.4 mM), niflumic acid (10(-5)-10(-4) M) or 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 10(-4)-5 x 10(-4) M) inhibited the generation of SWs and STDs, suggesting an involvement of chloride channels. 6 Application of nominally Ca2+ free solution, 5 x 10(-5) M BAPTA-AM, 10(-5) M cyclopiazonic acid, 10(-2) M caffeine or 10(-3) M procaine inhibited the generation of SWs and STDs, indicating that Ca2+ released from intracellular stores was required for the generation of SWs and STDs. 7 Exogenously applied noradrenaline (10(-7)-10(-5) M) increased the frequency of SWs through stimulation of a-adrenoceptors which was inhibited by sodium nitroprusside (SNP, 10(-4) M). SNP also reduced the frequency of SWs without altering the membrane potential, an effect mimicked by 8-bromocyclic GMP (10(-3) M) indicating that SNP acted by elevating the production of cyclic GMP. 8 It is concluded that smooth muscle cells of the rabbit urethra exhibit SWs and STDs which are likely to be induced by stimulation of Ca2+-activated chloride channels evoked by release of Ca2+ from intracellular stores.