6 research outputs found
TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?
The study of transient receptor potential (TRP) channels has dramatically increased during
the past few years. TRP channels function as sensors and effectors in the cellular adaptation to
environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6.
TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the
proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of
the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2
gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific
physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role
in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in
tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to
better understand certain renal disorders and ultimately create new therapeutic targets to improve
patient care
Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ : A Novel CT-Guided Approach to the Cochlea
TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is
still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The
purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone
pairs were excised from ten body donors, and the inner ear was first assessed based on computed
tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the
spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique
report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical
role of TRPC channels in human cochlear health and disease which has been suggested in previous
rodent experiments
TRPC6 Is Found in Distinct Compartments of the Human Kidney
In the context of renal proteinuric diseases, TRPC6 has been shown to play an important
role in ultrafiltration associated with the slit diaphragm through the control of the intracellular Ca2+
concentration in the podocytes of glomeruli. However, to date, the properties of TRPC6 have been
studied mainly in cell lines or in animal models. Therefore, the aim of the study presented here was to
investigate the presence and distribution of TRPC6 in human kidneys in order to possibly verify the
applicability of the results previously obtained in nonhuman experiments. For this purpose, kidneys
from nine cadavers were prepared for immunohistochemical staining and were supplemented with a
fresh human kidney obtained by nephrectomy. TRPC6 was detected in glomeruli and in the parietal
epithelial cells of Bowman’s capsule. Larger amounts were detected in the tubular system and
collecting ducts. In contrast to the peritubular capillary bed, which showed no immune reaction, the
cortical resistance vessels showed mild TRPC6 staining. In conclusion, our studies on the expression
of TRPC6 in human kidney tissue support the translational concept of the involvement of TRPC6 in
various renal diseases and reveal new aspects of the distribution of TRPC6 in the human kidney
TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?
The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care
Postmortem sympathomimetic iris excitability
Background:: A reliable estimation of time since death can be important for the law enforcement authorities. The
compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to
further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly
assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic
agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug
phenylephrine.
Methods:: Cadavers were included after body donors gave written informed consent during lifetime. Exclusion
criteria were known eye disease, or a postmortem interval exceeding 26 hours. A pupillometer with a minimum
measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 minutes after
the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil
diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction.
Results:: 30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was
in median 3.5 mm (interquartile range [IQR]: 3.0–4.5 mm) and progressed to 4.0 mm (IQR: 3.5–5.0 mm)
20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR:
0.0–1.0 mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and
paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the
initial and the reactive pupil (P = 0.0002).
Conclusion:: Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the
application of a third agent with a sympathomimetic mechanism of action could provide additional information.
Further studies assessing such a triple approach in the compound method in comparison with the current gold
standard for estimation of time since death are mandatory to ensure reliable results
TRPC3 Is Downregulated in Primary Hyperparathyroidism
Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a
critical role in calcium homeostasis. However, there are no established findings in this respect with
regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation,
little is known about the protein distribution of TRPC channels—especially TRPC3 and TRPC6—in
this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6
in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy
parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were
investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and
TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our
knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is
found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue
(pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and
TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence
indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion
regulation. These findings ultimately require further research in order to not only confirm our results
but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the
aforementioned physiological functions and pathophysiological conditions