Department of Anesthesiology and Intensive Care Medicine Nippon Medical School, Tokyo, Japan.
Adv Exp Med Biol. 2010;669:195-9. doi: 10.1007/978-1-4419-5692-7_39.
The possible roles of different potassium channels in oxygen sensing mechanisms of the carotid body are still not well defined. It has been suggested that leak potassium (K(+)) channels, voltage gated K(+) channels (Kv) and Ca(2+) dependent large conductance K(+) channels (BK) play important roles in the peripheral chemo-sensing mechanisms of the carotid body. In the present study, we have made an attempt to clarify the extent to which, these channels are involved in such mechanisms using in vitro model of isolated rabbit carotid body. Selective TASK-1 channel blocker, anandamide (3 microM) induced stimulation of the carotid sinus nerve (CSN) activity, in a very similar pattern to normal hypoxic responses, with peak discharge rates of the CSN up to 63 +/- 21% of the hypoxic responses (n = 33), and no additional increase in the CSN activity was observed during the hypoxic stimulation with the co-application of anandamide (n = 6). On the other hand, inhibition of BK channels by TEA (5 mM, n = 6), was sub-maximum and typical hypoxic responses were preserved during the increased CSN activity induced by TEA (n = 7). Maximal stimulation of the CSN activity was obtained by blocking Kv channels with 4AP (2.5 mM, n = 15), which was refractory to the hypoxic response. However the hypoxic response reappeared during hyperpolarization (n = 12). We have found that the leak K(+) channels (TASK-1) seem to be importantly involved in the initiation of the oxygen sensing mechanisms of the rabbit carotid body.
不同钾通道在颈动脉体氧感受机制中的可能作用仍未完全明确。有研究提示,漏钾(K(+)) 通道、电压门控 K(+) 通道(Kv)和 Ca(2+) 依赖性大电导 K(+) 通道(BK)在颈动脉体外周化学感受机制中发挥重要作用。在本研究中,我们试图采用分离的兔颈动脉体体外模型来阐明这些通道在这些机制中所起作用的程度。选择性 TASK-1 通道阻滞剂,花生四烯酸酰胺(3 μM)诱导颈动脉窦神经(CSN)活性刺激,其模式与正常低氧反应非常相似,CSN 的峰值放电率高达低氧反应的 63±21%(n=33),并且在花生四烯酸酰胺共应用时,CSN 活性没有进一步增加(n=6)。另一方面,BK 通道被 TEA(5 mM,n=6)抑制,为次最大抑制,并且在 TEA 诱导的 CSN 活性增加期间保留典型的低氧反应(n=7)。通过用 4AP(2.5 mM,n=15)阻断 Kv 通道可获得 CSN 活性的最大刺激,其对低氧反应无反应。然而,在超极化期间低氧反应再次出现(n=12)。我们发现,漏钾(K(+)) 通道(TASK-1)似乎在兔颈动脉体氧感受机制的启动中具有重要作用。