Ageing causes cytoplasmic retention of MaxiK channels in rat corporal smooth muscle cells.
The MaxiK channel plays a critical role in the regulation of corporal smooth muscle tone and thereby erectile function. Given that ageing results in a decline in erectile function, we determined changes in the expression of MaxiK, which might impact erectile function. Quantitative-polymerase chain reaction demonstrated that although there is no significant change in transcription of the alpha- and beta-subunits that comprise the MaxiK channel, there are significant changes in the expression of transcripts encoding different splice variants. One transcript, SV1, is 13-fold increased in expression in the ageing rat corpora. SV1 has previously been reported to trap other isoforms of the MaxiK channel in the cytoplasm. Correlating with increased expression of SV1, we observed in older rats there is approximately a 13-fold decrease in MaxiK protein in the corpora cell membrane and a greater proportion is retained in the cytoplasm (approximately threefold). These experiments demonstrate that ageing of the corpora is accompanied by changes in alternative splicing and cellular localization of the MaxiK channel.
Davies
K P
KP
Department of Urology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kdavis@aecom.yu.edu
Stanevsky
Y
Y
Tar
M T
MT
Moses
T
T
Chang
J S
JS
Chance
M R
MR
Melman
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D010413:Penis / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism
D018076:DNA, Complementary; D051036:Large-Conductance Calcium-Activated Potassium Channels