Functional expression of SK channels in murine detrusor PDGFRα<sup>+</sup> cells

Lee, Haeyeong; Koh, Byoung H.; Peri, Lauren E.; Sanders, Kenton M.; Koh, Sang Don

doi:10.1113/jphysiol.2012.241505

Cited by 56 publications

(101 citation statements)

References 21 publications

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“…It is also important to consider that BK channels appear to be restricted to UBSM cells with no detectable expression in other components of the UBSM layer. Indeed, BK channels are not functionally expressed in the bladder nerves within the bladder wall (150) or in mouse bladder interstitial cells known as plateletderived growth factor receptor-␣ (PDGFR␣ ϩ ) cells (83). Penitrem A-sensitive outward currents, with properties characteristic similar to BK currents have been reported in guinea pig detrusor interstitial cells (90).…”

Section: Ubsm Bk Channel Therapeutic Potential For Lutsmentioning

confidence: 98%

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

Petkov

2014

American Journal of Physiology-Regulatory, Integrative and Comp

133

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The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, which comprises the bladder wall. The large-conductance voltage- and Ca(2+)-activated K(+) (BK, BKCa, MaxiK, Slo1, or KCa1.1) channel is highly expressed in UBSM and is arguably the most important physiologically relevant K(+) channel that regulates UBSM function. Its significance arises from the fact that the BK channel is the only K(+) channel that is activated by increases in both voltage and intracellular Ca(2+). The BK channels control UBSM excitability and contractility by maintaining the resting membrane potential and shaping the repolarization phase of the spontaneous action potentials that determine UBSM spontaneous rhythmic contractility. In UBSM, these channels have complex regulatory mechanisms involving integrated intracellular Ca(2+) signals, protein kinases, phosphodiesterases, and close functional interactions with muscarinic and β-adrenergic receptors. BK channel dysfunction is implicated in some forms of bladder pathologies, such as detrusor overactivity, and related overactive bladder. This review article summarizes the current state of knowledge of the functional role of UBSM BK channels under normal and pathophysiological conditions and provides new insight toward the BK channels as targets for pharmacological or genetic control of UBSM function. Modulation of UBSM BK channels can occur by directly or indirectly targeting their regulatory mechanisms, which has the potential to provide novel therapeutic approaches for bladder dysfunction, such as overactive bladder and detrusor underactivity.

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Section: Ubsm Bk Channel Therapeutic Potential For Lutsmentioning

confidence: 98%

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

Petkov

2014

American Journal of Physiology-Regulatory, Integrative and Comp

133

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“…PDGFRalpha þ CELLS IN THE FEMALE REPRODUCTIVE TRACT receptor and SK3 channels [16], suggested involvement in purinergic neuroeffector responses [43]. Interestingly, some PDGFRa þ cells in the bladder were reported to be vimentin and Kit positive, suggesting possible diversity in this type of interstitial cell in bladder and GI muscles [17].…”

Section: Peri Et Almentioning

confidence: 96%

“…Interstitial cells immunopositive for PDGFRa have also been discovered in the muscularis of the bladder [15][16][17]. PDGFRa þ cells are distinct from nerve elements, ICCs, and SMCs [12][13][14].…”

Section: Introductionmentioning

confidence: 97%

A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

Peri¹,

Koh²,

Ward³

et al. 2015

Biology of Reproduction

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Growing evidence suggests important roles for specialized platelet-derived growth factor receptor alpha-positive (PDGFRalpha(+)) cells in regulating the behaviors of visceral smooth muscle organs. Examination of the female reproductive tracts of mice and monkeys showed that PDGFRalpha(+) cells form extensive networks in ovary, oviduct, and uterus. PDGFRalpha(+) cells were located in discrete locations within these organs, and their distribution and density were similar in rodents and primates. PDGFRalpha(+) cells were distinct from smooth muscle cells and interstitial cells of Cajal (ICC). This was demonstrated with immunohistochemical techniques and by performing molecular expression studies on PDGFRalpha(+) cells from mice with enhanced green fluorescent protein driven off of the endogenous promoter for Pdgfralpha. Significant differences in gene expression were found in PDGFRalpha(+) cells from ovary, oviduct, and uterus. Differences in gene expression were also detected in cells from different tissue regions within the same organ (e.g., uterine myometrium vs. endometrium). PDGFRalpha(+) cells are unlikely to provide pacemaker activity because they lack significant expression of key pacemaker genes found in ICC (Kit and Ano1). Gja1 encoding connexin 43 was expressed at relatively high levels in PDGFRalpha(+) cells (except in the ovary), suggesting these cells can form gap junctions to one another and neighboring smooth muscle cells. PDGFRalpha(+) cells also expressed the early response transcription factor and proto-oncogene Fos, particularly in the ovary. These data demonstrate extensive distribution of PDGFRalpha(+) cells throughout the female reproductive tract. These cells are a heterogeneous population of cells that are likely to contribute to different aspects of physiological regulation in the various anatomical niches they occupy.

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“…72,73 These channels have also been implicated in bladder ICC function. 74 Intermediate-conductance, calciumactivated K C (IK Ca ) channels have not yet been found to be functionally important in bladder smooth muscle cells, 75 although they have been detected at the transcriptional and protein levels.…”

Section: Possible Roles For Other Kmentioning

confidence: 99%

Ion channels of the mammalian urethra

Kyle

2014

Channels

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Functional expression of SK channels in murine detrusor PDGFRα⁺ cells

Cited by 56 publications

References 21 publications

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

Ion channels of the mammalian urethra

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Functional expression of SK channels in murine detrusor PDGFRα+ cells

Cited by 56 publications

References 21 publications

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

Ion channels of the mammalian urethra

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Functional expression of SK channels in murine detrusor PDGFRα⁺ cells