PURPOSE: Although L-type Ca2+ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca2+ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca2+ channels to myogenic signaling in arterioles of the rat retinal microcirculation. METHODS: Confocal immunolabeling of whole-mount preparations was used to investigate the localization of CaV3.1-3 channels in retinal arteriolar smooth muscle cells. T-type currents and the contribution of T-type channels to myogenic signaling were assessed by whole-cell patch-clamp recording and pressure myography of isolated retinal arteriole segments. RESULTS: Strong immunolabeling for CaV3.1 was observed on the plasma membrane of retinal arteriolar smooth muscle cells. In contrast, no expression of CaV3.2 or CaV3.3 could be detected in retinal arterioles, although these channels were present on glial cell end-feet surrounding the vessels and retinal ganglion cells, respectively. TTA-A2-sensitive T-type currents were recorded in retinal arteriolar myocytes with biophysical properties distinct from those of the L-type currents present in these cells. Inhibition of T-type channels using TTA-A2 or ML-218 dilated isolated, myogenically active, retinal arterioles. CONCLUSIONS: CaV3.1 T-type Ca2+ channels are functionally expressed on arteriolar smooth muscle cells of retinal arterioles and play an important role in myogenic signaling in these vessels. The work has important implications concerning our understanding of the mechanisms controlling blood flow autoregulation in the retina and its disruption during ocular disease.
PURPOSE: Although L-type Ca2+ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca2+ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca2+ channels to myogenic signaling in arterioles of the rat retinal microcirculation. METHODS: Confocal immunolabeling of whole-mount preparations was used to investigate the localization of CaV3.1-3 channels in retinal arteriolar smooth muscle cells. T-type currents and the contribution of T-type channels to myogenic signaling were assessed by whole-cell patch-clamp recording and pressure myography of isolated retinal arteriole segments. RESULTS: Strong immunolabeling for CaV3.1 was observed on the plasma membrane of retinal arteriolar smooth muscle cells. In contrast, no expression of CaV3.2 or CaV3.3 could be detected in retinal arterioles, although these channels were present on glial cell end-feet surrounding the vessels and retinal ganglion cells, respectively. TTA-A2-sensitive T-type currents were recorded in retinal arteriolar myocytes with biophysical properties distinct from those of the L-type currents present in these cells. Inhibition of T-type channels using TTA-A2 or ML-218 dilated isolated, myogenically active, retinal arterioles. CONCLUSIONS: CaV3.1 T-type Ca2+ channels are functionally expressed on arteriolar smooth muscle cells of retinal arterioles and play an important role in myogenic signaling in these vessels. The work has important implications concerning our understanding of the mechanisms controlling blood flow autoregulation in the retina and its disruption during ocular disease.
Authors: Udaiyappan Janakiraman; Jie Yu; Aubin Moutal; Dhanalakshmi Chinnasamy; Lisa Boinon; Shelby N Batchelor; Annaduri Anandhan; Rajesh Khanna; Mark A Nelson Journal: Neurobiol Dis Date: 2019-07-22 Impact factor: 5.996
Authors: Tim M Curtis; Declan McLaughlin; Michael O'Hare; Joanna Kur; Peter Barabas; Gordon Revolta; C Norman Scholfield; J Graham McGeown; Mary K McGahon Journal: J Vis Exp Date: 2018-07-14 Impact factor: 1.355
Authors: Eric A Pereira da Silva; Miguel Martín-Aragón Baudel; Manuel F Navedo; Madeline Nieves-Cintrón Journal: Front Physiol Date: 2022-08-26 Impact factor: 4.755