Potassium (K) channels are important modulators of vascular smooth muscle tone. In isolated tissues and cultured cells derived from the trabecular smooth muscle of the human corpora, two K channel subtypes in particular, the maxi-K and K/ATP, respectively, have been identified. The activity of these two K channel subtypes is modulated by a host of physiologically relevant endogenous neurotransmitters, neuromodulators and hormones. These observations reflect that fact that these K channel subtypes are a convergence point for the regulation of both contractile and relaxation responses. As such, these K channels can be regarded as a final common effector of corporal smooth muscle tone, and thus, of erectile capacity. Therefore, it is likely that alterations in K channel function may be responsible, at least in part, for both the heightened corporal smooth muscle contractility and the impaired smooth muscle relaxation thought to be a prevalent aspect of erectile dysfunction in a large proportion of impotent men. The goal of this proposal is to explore and characterize the physiology and pathophysiology of the regulation and function of these two prominent K+ currents in isolated tissue strips and explant cultured and enzymatically dissociated smooth muscle cells derived from the corpus cavernosum of potent men, as well as men with organic erectile dysfunction. Specifically, we shall: 1) Evaluate the contribution of the maxi-K and K/ATP channels to contractile responses elicited by phenylephrine (PE) and endothelin-1 (ET-1) on isolated corporal tissue strips. 2) Evaluate the contribution of K channels to relaxation responses in isolated corporal smooth muscle strips precontracted with PE or ET-1. 3) Examine the effects of K channel activation/blockade on resting and receptor-mediated increases in intracellular calcium levels in enzymatically dissociated and cultured human corporal smooth muscle cells. 4) transfect isolated corporal tissue strips and cultured corporal smooth muscle cells with the human maxi-K channel cDNA (hSlo), and evaluate the effects of transfection .

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042027-12
Application #
6164522
Study Section
Special Emphasis Panel (ZRG4-GMB (05))
Program Officer
Nyberg, Leroy M
Project Start
1989-03-01
Project End
2001-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
12
Fiscal Year
2000
Total Cost
$260,351
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Urology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Spektor, Mariya; Rodriguez, Ramon; Rosenbaum, Raymond S et al. (2002) Potassium channels and human corporeal smooth muscle cell tone: further evidence of the physiological relevance of the Maxi-K channel subtype to the regulation of human corporeal smooth muscle tone in vitro. J Urol 167:2628-35
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Fan, S F; Christ, G J; Melman, A et al. (1999) A stretch-sensitive Cl- channel in human corpus cavernosal myocytes. Int J Impot Res 11:1-7
Lee, S W; Wang, H Z; Christ, G J (1999) Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells. Int J Impot Res 11:179-88

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