Ryanodine receptors in human bladder smooth muscle

Abstract

SUMMARY The role of intracellular Ca2+ release in the activation of human bladder smooth muscle is controversial. We have measured the expression of mRNA encoding for the ryanodine receptor (RyR) isoforms (RyR1, RyR2 and RyR3) in isolated human detrusor smooth muscle. mRNA for RyR2 was detected in all samples but no mRNA for RyR1 or RyR3 could be found. Human bladder smooth muscle cells in culture are unresponsive to caffeine, suggesting the absence of a functional RyR system. However, mRNA encoding for RyR2 was detected in these cells. Using saponin‐permeabilized cells, a Ruthenium Red‐sensitive Ca2+‐dependent 45Ca2+ release could be demonstrated from the sarcoplasmic reticulum (SR). These data confirm the functional presence of Ca2+‐induced Ca2+ release (CICR) in cells and suggest that the properties of the RyR2 isoform in human detrusor may change when the cells are maintained in culture. The implications of these observations to detrusor smooth muscle function are discussed.

Intracellular Ca2+ regulation in a human prostate stromal cell culture

“…This is also similar to primary detrusor smooth muscle cells, but di¡erent from their cultured counterparts where ca¡eine responses are signi¢cantly reduced [Chambers et al, 1999]. The existence of functional ryanodine receptor-Ca 2þ release channels has important implications: these channels act as Ca 2þ oscillators to produce regenerative Ca 2þ -transients [Jaggar et al, 2000] ] i occurred when the myocyte was electrically depolarised [Eckert et al, 1995].…”

Human Isolated Bronchial Smooth Muscle Contains Functional Ryanodine/Caffeine–sensitive Ca-Release Channels

“…However, in contrast to the situation in human cerebellum and skeletal muscle, only the ryr3 mRNA isoform is expressed in the bronchus. This is an original feature of HBSM because alternative distributions of RyRs have been characterized in a number of other animal smooth muscles, i.e., porcine trachea, rat myometrium, rat vessels (9,28,29) or even human smooth muscles, i.e., bladder (30). This specificity in the isoform distribution may have important functional consequences.…”

Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells

“…71 In cardiac myocytes, Ca V channels on the SR are physiologically coupled to RyRs on the SR membrane whereby a small amount of extracellular Ca 2C influx through Ca V channels activates RyR2 to induce a massive Ca 2C release from the SR, i.e., Ca 2C -induced Ca 2C release (CICR), which is required for physiological cardiac functions, 73,74 RyR2 may play a crucial role in the regulation of Ca 2C and contractile responses during the excitation-contraction coupling in UBSMCs. 71,75 Reportedly, a loose coupling between Ca V channels and RyRs exists in UBSMCs, in which Ca 2C influx due to the opening of single Ca V channels is insufficient to activate RyRs to induce Ca 2C release; rather, aggregate Ca 2C influx via a number of Ca V channels must be large enough to open RyRs. 76,77 An interpretation for this loose coupling is that RyR2 may show a lesser Ca 2C sensitivity in UBSMCs than in cardiac muscle.…”

“…69,70 It has been reported that RyR2, but not RyR1 or RyR3, mRNAs are expressed in freshly isolated and cultured human UBSMCs. 71 However, RyR2 mRNA expression is undetected following culture, suggesting that properties of the RyR2 isoform in human UBSMCs may change when the cells are maintained in culture. 71 The importance of RyRs to regulate the spontaneous phasic contractions has been demonstrated using a rat model of partial bladder outlet obstruction (PBOO).…”

“…71 However, RyR2 mRNA expression is undetected following culture, suggesting that properties of the RyR2 isoform in human UBSMCs may change when the cells are maintained in culture. 71 The importance of RyRs to regulate the spontaneous phasic contractions has been demonstrated using a rat model of partial bladder outlet obstruction (PBOO). 72 These animals develop overactive UBSMC contraction that is associated with a significant decrease in expression and activity of RyRs.…”