[Voltage-dependent potassium channel and calcium-activated potassium channel current changes of peripheral blood T-lymphocytes from hypertensive patients in Xinjiang Kazakh].

OBJECTIVE: To observe the current changes of voltage-dependent potassium channel (Kv1.3 potassium channel) and calcium-activated potassium channel (IKCa1 potassium channel) in peripheral blood T-lymphocyte derived from hypertensive patients of Xinjiang Kazakh. METHODS: Twenty randomly selected untreated Kazakh hypertensive patients and 20 Kazakh healthy subjects from Xinjiang were included in this study. T-lymphocytes were isolated from peripheral blood with magnetic cell sorting, the whole-cell currents of Kv1.3 and IKCa1 potassium channels were recorded with patch-clamp technique. RESULTS: (1) The current density of Kv1.3 potassium channel was significantly higher in the hypertensive group [(280 ± 74) pA/pF (n = 39)] than that in the control group [(179 ± 51) pA/pF (n = 38), P < 0.01], while the membrane capacitance was similar between the two groups. (2) The current density of IKCa1 potassium channel was also significantly higher in the hypertensive group [(198 ± 44) pA/pF (n = 28)] than that in the control group [(124 ± 43) pA/pF (n = 26), P < 0.01], while the membrane capacitance was also similar between the two groups. CONCLUSIONS: The T-lymphocytes Kv1.3 potassium channel and IKCa1 potassium channel current densities are higher in hypertensive patients in Xinjiang Kazakh suggesting a potential role of Kv1.3 and IKCa1 potassium channels activation in the pathophysiology of hypertension.

T-lymphocyte Kv1.3 channel activation triggers the NLRP3 inflammasome signaling pathway in hypertensive patients.

The aim of the current study was to investigate the correlation between voltage-gated potassium 1.3 (Kv1.3) channel of peripheral blood T-lymphocytes and the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in hypertensive patients. Peripheral blood samples from the hypertensive Kazakh patients (n=30) and healthy Kazakh subjects (n=30) were collected. The T lymphocytes and serum were separated, and the state of Kv1.3 channels was detected using the patch-clamp technique. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression levels of key molecules [NLRP3, caspase-1 and interleuking (IL)-ß] in the lymphocyte NLRP3 inflammasome pathway, while serum IL-1ß content was measured by ELISA assay. The results demonstrated no statistical difference in the subject baseline data between the two groups. While more significantly activated Kv1.3 channels were identified in the peripheral blood T-lymphocytes of the hypertension group compared to the normotension group, the mRNA and protein expression levels of NLRP3, caspase-1 and IL-1ß were elevated and their peripheral serum interleukin-1ß levels were significantly increased. After inhibiting the Kv1.3 channels using the classic potassium channel blocker, these indicators were all decreased significantly. The results indicate that the NLRP3 inflammasome pathway of peripheral blood T-lymphocytes in hypertensive Kazakh patients is activated, which may be correlated with the opening of the Kv1.3 channel.

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension.

INTRODUCTION: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. METHODS: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL)-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA) and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. RESULTS: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. CONCLUSIONS: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.