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

Abstract

. Intracellular microelectrode recordings were made from circular smooth muscle of rabbit urethra. . 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. . 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. . Application of 3 × 10−6 m nifedipine or 5 × 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. . 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 × 10−4 m) inhibited the generation of SWs and STDs, suggesting an involvement of chloride channels. . Application of nominally Ca2+ free solution, 5 × 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. . Exogenously applied noradrenaline (10−7‐10−5 m) increased the frequency of SWs through stimulation of α‐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. . 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.

Ca2+-activated Cl− current in sheep lymphatic smooth muscle

“…The above results support the idea that a Ca 2ϩ -activated Cl Ϫ conductance underlies the STDs and initiates the action potentials in our single cell experiments. Similar STDs and action potentials have also been recorded in the urethra of sheep and rabbits (8,16,17). In both of these tissues, it has been suggested that Ca 2ϩ release from the sarcoplasmic reticulum is responsible for the activation of the Cl Ϫ current that in turn depolarizes the membrane and elicits Ca 2ϩ action potentials.…”

ET‐1‐associated vasomotion and vasospasm in lymphatic vessels of the guinea‐pig mesentery

“…Importantly, caffeine (10 mM) abolished spontaneous vasomotion and the enhancement of both vasomotion and tonic [Ca 2 þ ] i induced by 1 nM ET-1 (n ¼ 6; Figure 7Bc). This is a common action of caffeine, as observed for electrical rhythmicities in other smooth muscles (Hashitani et al, 1996;van Helden et al, 2000), and is likely to occur through its known actions to inhibit IP 3 R-mediated Ca 2 þ release (Ehrlich & Watras, 1988) and/or to increase cAMP (Beavo & Reifsnyder, 1990). …”

A survey of commonalities relevant to function and dysfunction in pelvic and sexual organs

“…40,41 As in the gut, this activity is not seen in isolated myocytes, but is generated in interstitial cells, 42 and here they may have a genuine pacemaker role. The mechanical characteristics of the urethral smooth muscle strips, which display sustained tone, however, are clearly different from the isolated slow waveassociated contractions seen in the gut.…”

“…In the rabbit urethra, sodium nitroprusside, an NO donor, modestly reduced the frequency of spontaneous slow waves without changing the membrane potential. 41 In the same tissue, neither exogenous NO nor transmural nerve stimulation had any effect on spontaneous electrical activity. 67 Therefore, it seems to be unlikely that NO relaxes the urethral smooth muscles by diminishing electrical activity through membrane hyperpolarization.…”