Physiology and Pharmacology Ca V 3.1 T-Type Ca 2þ Channels Contribute to Myogenic Signaling in Rat Retinal Arterioles

Abstract

PURPOSE. Although L-type Ca 2þ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca 2þ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca 2þ 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 Ca V 3.1-3 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 patchclamp recording and pressure myography of isolated retinal arteriole segments. RESULTS. Strong immunolabeling for Ca V 3.1 was observed on the plasma membrane of retinal arteriolar smooth muscle cells. In contrast, no expression of Ca V 3.2 or Ca V 3.3 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. Ca V 3.1 T-type Ca 2þ 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

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