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2016 ; 228
(5
): 812-25
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Hyperpolarization-activated cation and T-type calcium ion channel expression in
porcine and human renal pacemaker tissues
#MMPMID26805464
Hurtado R
; Smith CS
J Anat
2016[May]; 228
(5
): 812-25
PMID26805464
show ga
Renal pacemaker activity triggers peristaltic upper urinary tract contractions
that propel waste from the kidney to the bladder, a process prone to congenital
defects that are the leading cause of pediatric kidney failure. Recently, studies
have discovered that hyperpolarization-activated cation (HCN) and T-type calcium
(TTC) channel conductances underlie murine renal pacemaker activity, setting the
origin and frequency and coordinating upper urinary tract peristalsis. Here, we
determined whether this ion channel expression is conserved in the porcine and
human urinary tracts, which share a distinct multicalyceal anatomy with multiple
pacemaker sites. Double chromagenic immunohistochemistry revealed that HCN
isoform 3 is highly expressed at the porcine minor calyces, the renal pacemaker
tissues, whereas the kidney and urinary tract smooth muscle lacked this HCN
expression. Immunofluorescent staining demonstrated that HCN(+) cells are
integrated within the porcine calyx smooth muscle, and that they co-express TTC
channel isoform Cav3.2. In humans, the anatomic structure of the minor calyx
pacemaker was assayed via hematoxylin and eosin analyses, and enabled the
visualization of the calyx smooth muscle surrounding adjacent papillae.
Strikingly, immunofluorescence revealed that HCN3(+) /Cav3.2(+) cells are also
localized to the human minor calyx smooth muscle. Collectively, these data have
elucidated a conserved molecular signature of HCN and TTC channel expression in
porcine and human calyx pacemaker tissues. These findings provide evidence for
the mechanisms that can drive renal pacemaker activity in the multi-calyceal
urinary tract, and potential causes of obstructive uropathies.
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