Abstract
MechanoTRP channels may play a role in the pressureinduced vasoconstriction or ‘myogenic response’ by acting as
a pathway for depolarisation and Ca2+
-entry in vascular
smooth muscle. Here we present evidence that TRPV2 forms
a mechanoTRP channel in retinal arteriolar smooth muscle
cells (SMCs) which contributes to the generation of
myogenic signalling in this tissue. Using RT-PCR and
immunohistochemistry (IHC) a number of known mechanoTRP channels were identified in rat retinal arteriolar SMCs.
Stretch sensitive responses in isolated arterioles were tested
(fura-2 microfluorimetry and whole-cell patch-clamp) by
reducing external osmolarity and by application of negative
pressure (cell-attached patch-clamp). Myogenic tone was
investigated in isolated pressurised arteriolar segments.
mRNA transcripts for TRPC1, M7, V1, V2, V4 and P1
channels were detected. In contrast to larger resistance
arteries, retinal arterioles do not appear to express TRPC6 or
M4 channels. IHC revealed cytosolic and membrane expression of TRPC1, M7, V1, V2 and P1 in SMCs surrounding
arterioles; TRPV4 expression was more prominent in the
SMC nucleus than cytosol. Hypo-osmotic stretch increased
[Ca2+
]i (dependent on external Ca2+
) which was reversed by
the TRPV2 inhibitor tranilast (100 lM; n = 5) and the nonselective TRPP1/V2 antagonist amiloride (100 lM; n = 8).
Inhibitors of TRPC1, M7, V1 and V4 had no effect. Hypoosmotic stretch activated currents were not consistent with
activation of TRPP1 channels. Pressure-induced stretch
resulted in an increase in channel activity which was absent
in the presence of tranilast. Application of tranilast to
pressurised retinal arterioles resulted in significant dilation
(n = 9; p < 0.001, paired t-test). Our results suggest that rat
retinal arteriolar SMCs express a range of mechanoTRP
channels however only TRPV2 channels were found to
function as mechanosensors under these conditions. Thus
TRPV2 channels represent molecular candidates underpinning the myogenic response in this vascular bed.
Original language | English |
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Pages | 753-781 |
Number of pages | 1 |
Publication status | Published - 17 Apr 2015 |
Event | The British Microcirculation Society 65th annual meeting - University of Manchester, Manchester, United Kingdom Duration: 16 Apr 2015 → 17 Apr 2015 https://onlinelibrary.wiley.com/doi/pdf/10.1111/micc.12212 |
Conference
Conference | The British Microcirculation Society 65th annual meeting |
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Country/Territory | United Kingdom |
City | Manchester |
Period | 16/04/2015 → 17/04/2015 |
Internet address |