Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function.
The Ca2+-sensitive K+ channel (maxi-K+) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: 1) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K+ channel, and 2) to determine whether transfection of the maxi-K+ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMVbeta/Lac Z DNA in 10-wk-old rats resulted in significant incorporation and expression of beta-galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N = 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N = 5) and 2 mo (N = 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N = 2) and 4 mo (N = 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.
Department of Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
G J
GJ
Christ
J
J
Rehman
N
N
Day
L
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Salkoff
M
M
Valcic
A
A
Melman
J
J
Geliebter
D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004558:Electric Stimulation; D018014:Gene Transfer Techniques; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008845:Microinjections; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000294:innervation / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D018076:DNA, Complementary; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase