The effects of pH changes on human and ferret detrusor muscle function.

Abstract

1. The effects of altering extracellular pH on the electrically evoked contractions of ferret and human bladder (detrusor) smooth muscle have been investigated. pH was varied by changing superfusate PCO2 or NaHCO3 concentration. Acidosis increased force when superfusate PCO2 was raised but decreased force when the NaHCO3 concentration was reduced. 2. Intracellular pH (pHi) in isolated ferret detrusor cells was measured separately by epifluorescence microscopy. Extracellular pH changes caused by altering superfusate PCO2 were accompanied by similar changes of pHi, whereas variation of the NaHCO3 concentration had smaller effects on pHi. 3. It was proposed that intracellular acidosis increased contraction but extracellular acidosis depressed contraction. 4. Other interventions, such as addition and removal of NH4Cl, Cl- replacement, and NaHCO3 replacement with HEPES, changed pHi and had predictable effects on force. It was possible to describe unique relationships between tension and either intracellular or extracellular pH regardless of the means whereby pH changes were brought about. 5. Resting tension was reduced whether brought about by either intracellular or extracellular acidosis. K+ contractures were similarly affected by acidosis. Ferret preparations showed low levels of spontaneous activity, which was reduced by acidosis and enhanced by alkalosis.

The effects of extracellular and intracellular pH on intracellular Ca2+ regulation in guinea‐pig detrusor smooth muscle

“…Actions of H¤ on detrusor smooth muscle A pHé value of 7·10 in guinea-pig detrusor myocytes (Table 1) is similar to that reported for human and ferret detrusor myocytes (Liston et al 1991;Fry et al 1994b). The sustained nature of the pHé change when superfusate PCOµ was altered and the lack of effect upon changes to superfusate [NaHCO×] at constant PCOµ measured in this study is in contrast to observations in some other smooth muscles (Aickin & Brading, 1984;Aalkjòr & Cragoe, 1988;Austin & Wray, 1993) and may reflect different pH-regulating mechanisms or surface membrane permeability to H¤ between detrusor and these other muscles.…”

“…The sustained nature of the pHé change when superfusate PCOµ was altered and the lack of effect upon changes to superfusate [NaHCO×] at constant PCOµ measured in this study is in contrast to observations in some other smooth muscles (Aickin & Brading, 1984;Aalkjòr & Cragoe, 1988;Austin & Wray, 1993) and may reflect different pH-regulating mechanisms or surface membrane permeability to H¤ between detrusor and these other muscles. nerves embedded in the tissue or by direct electrical stimulation of the muscle (Liston et al 1991). In this study, extracellular acidosis was negatively inotropic, a finding similar to that in cardiac and several other smooth muscles (Wray, 1988;Orchard & Kentish, 1990); however, intracellular acidification increased the force of phasic contractions.…”

“…The relationship between the carbachol-induced Ca¥ transient and contraction A previous study (Liston et al 1991) established the relationship between the magnitude of phasic isometric detrusor contractions and the value of either pHï or pHé. It was found that intracellular acidosis increases, while extracellular acidosis decreases, the force of contraction.…”

“…However, several lines of evidence indicate that this is unlikely: (i) the increase in force by decreased pHé is unaffected by amiloride or DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid; Liston et al 1991), (ii) the importance of Na¤-Ca¥ exchange in guinea-pig detrusor is questionable (Ganitkevich & Isenberg, 1991), and (iii) intracellular acidosis did not modulate the rate of recovery of [Ca¥]é on return from a zero-Ca¥ superfusate (Fig. 9).…”

Renal Physiology

“…Fry Division of Physiology, UMDS, London SE1 7EH Hydrodistension of the bladder reduces blood flow to the organ (Siroky et al 1990). Changes to intracellular and extracellular pH have profound effects on detrusor smooth muscle contractility (Liston et al 1991) and in man urodynamic intravesical pressure measurements have been shown to be affected by the pH of the filling solution (Sethia & Smith, 1987). The aim of this present study was to determine whether intramural pH changes accompanied bladder wall ischaemia during bladder filling.…”