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1 Department of Urology, Albert Einstein College of Medicine, Bronx, New York 10461; and 2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
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
pCMV
/Lac Z DNA in 10-wk-old rats resulted in significant
incorporation and expression of -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.
corporal smooth muscle; neurostimulation; intracavernous pressure; relaxation; intracavernous injection
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