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Molecular and functional identificat...

University of Nevada, Reno., Cell and Molecular Pharmacology and Physiology.

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Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle./
Author:	Abu Baker, Salah.
Description:	291 p.
Notes:	Adviser: Sang Don Koh.
Contained By:	Dissertation Abstracts International69-08B.
Subject:	Biology, Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3320570
ISBN:	9780549738268

Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle.
Abu Baker, Salah.

Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle. - 291 p.

Adviser: Sang Don Koh.

Thesis (Ph.D.)--University of Nevada, Reno, 2008.

Purpose. A new distinct family of K+ channels, the two-pore K+ channels (K2P) has emerged. This class of K+ channels are implicated in several functions which include; regulating and setting membrane potential, K+ homeostasis, mediating responses to stretch, sensors for pH and O2, mediating responses to ischemia and they can act as targets for volatile and local anesthetics. Despite their important physiological role, the focus of previous work on these channels has mainly limited to neuronal function. Little is known about their molecular expression, diverse function and their implication in pathological conditions in smooth muscle tissues.

ISBN: 9780549738268Subjects--Topical Terms:

1017816
Biology, Physiology.

Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle.
LDR:03932nam 2200313 a 45 001 855223
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020 $a 9780549738268
035 $a (UMI)AAI3320570
035 $a AAI3320570
040 $a UMI $c UMI
100 1 $a Abu Baker, Salah. $3 1021776
245 1 0 $a Molecular and functional identification of the two-pore potassium ion channels in bladder smooth muscle.
300 $a 291 p.
500 $a Adviser: Sang Don Koh.
500 $a Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4599.
502 $a Thesis (Ph.D.)--University of Nevada, Reno, 2008.
520 $a Purpose. A new distinct family of K+ channels, the two-pore K+ channels (K2P) has emerged. This class of K+ channels are implicated in several functions which include; regulating and setting membrane potential, K+ homeostasis, mediating responses to stretch, sensors for pH and O2, mediating responses to ischemia and they can act as targets for volatile and local anesthetics. Despite their important physiological role, the focus of previous work on these channels has mainly limited to neuronal function. Little is known about their molecular expression, diverse function and their implication in pathological conditions in smooth muscle tissues.
520 $a To date the two-pore K+ channels have not been explored in the bladder field. Therefore, evaluation of their distribution and function in the bladder is essential. Thus, this dissertation is concerned with the K2P channel members, TASK and TREK expression and functional role in bladder physiology and pathological conditions including bladder ischemia, overactive bladder, bladder outlet obstruction and postmenopausal overactive bladder.
520 $a Results. Using molecular biology, protein chemistry, electrophysiology, Ca2+ imaging, confocal microscopy and cystometrics, we have investigated the expression of K2P channels (TASK-1& 2 and TREK-1) in bladder detrusor muscle and identified their functional role in this tissue. We determined that TASK-1 and TASK-2 channels encode the acidic pH-sensitive currents observed in bladder myocytes and that these channels mediate responses to bladder ischemic episodes. Furthermore, we demonstrated that TREK-1 channels encode the stretch-dependent K + channels in bladder smooth muscle, and formulated a novel hypothesis that these channels may be activated during detrusor stretch. During such conditions these channels will help to stabilize membrane potential to accommodate urine during progressive bladder filling.
520 $a We have also developed a murine model of partial bladder outlet obstruction (PBOO) which served as a powerful experimental model to evaluate the expression and functional fate of TREK-1 channels during bladder obstruction. Our studies clearly demonstrate that the TREK-1 malfunction is associated with channel down-regulation in PBOO, which in turn may explain the overactive detrusor phenotype observed in PBOO. We also investigated the contribution of TREK-1 channels to postmenopausal overactive bladder and demonstrated that TREK-1 expression is modulated by estrogen. Thus the low expression of TREK-1 due to estrogen deficiency may explain symptoms of detrusor overactivity observed in postmenopausal women.
520 $a Conclusions. The studies described in this dissertation provide new insights into the expression and functional role of K2P channels (TASK-1& 2 and TREK-1) in the bladder detrusor. By exploring their contribution to bladder excitability we have provided new directions which will aid in the development of new pharmaceutical targets in several bladder disorders.
590 $a School code: 0139.
650 4 $a Biology, Physiology. $3 1017816
690 $a 0719
710 2 $a University of Nevada, Reno. $b Cell and Molecular Pharmacology and Physiology. $3 1021775
773 0 $t Dissertation Abstracts International $g 69-08B.
790 $a 0139
790 1 0 $a Koh, Sang Don, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3320570