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.
Christ
G J
GJ
Department of Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Rehman
J
J
Day
N
N
Salkoff
L
L
Valcic
M
M
Melman
A
A
Geliebter
J
J
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