Gas exchange, ionoregulation, acid-base balance and their interactions in fish: The evolution of complex physiological systems.

我的研究计划的长期目标是了解气体交换，离子调节和酸碱平衡之间的相互作用，在鱼类环境驯化/适应和发展。在这个建议中，我将调查与酸碱调节相互作用的三个领域作为一个共同的主题，主要集中在“原始”和发展中的鱼类。1)鱼鳃是多功能的，包括气体交换，离子调节和酸碱平衡的主要表面，所有这些过程对生存至关重要。在一般情况下，脊椎动物鳃被认为是进化主要是为了增强气体交换和其他过程的次要，然而，根据我们最近的研究结果，我们假设脊椎动物鳃进化为酸碱调节第一，气体交换次要。2)虽然鳃是鱼类血液pH值调节的主要部位，但在高CO2水平下，它们的这种能力受到限制。能够耐受高CO2的鱼类似乎放弃了血液pH值调节，而是捍卫重要组织的pH值，我们称之为优先pH值（ppHi）调节。我们将研究ppHi调节的演变，其功能意义和细胞机制，我们假设它与鱼类呼吸空气的演变有关。3)硬骨鱼（占所有脊椎动物的一半）具有非常pH敏感的血红蛋白（根效应），其中专门结构中pH的降低大大增强了向眼睛和鱼鳔的O2输送，这被认为与硬骨鱼广泛的适应性辐射有关。然而，我们已经发现了一种机制，在存在Root效应的情况下，轻微的酸碱紊乱可以大大增强肌肉O2的输送。我们将进一步研究这一机制及其功能意义，以确定增强的总体O2输送是否可能代表鱼类根效应的早期选择。拟议的实验是跨学科的，跨越分子，细胞和整个动物的范围。它们旨在测试新的假设和发现将大大增加我们对复杂生理系统进化的理解，并有可能改变教科书的教条。

The long-term goal of my research program is to understand the interaction between gas-exchange, ion regulation and acid-base balance in fish during environmental acclimation/adaptation and development. In this proposal I will investigate three areas that interact with acid-base regulation as a common theme, with the focus largely upon "primitive" and developing fish. 1) The fish gill is multifunctional, comprising the dominant surface for gas exchange, ion regulation, and acid-base balance, all processes crucial for survival. In general, the vertebrate gill is thought to have evolved primarily to enhance gas exchange and secondarily for other processes, however, based upon our recent findings we hypothesize that the vertebrate gill evolved for acid-base regulation first, and gas exchange secondarily. 2) While the gills are the primary site for blood pH regulation in fish, they become limited in this capacity at high CO2 levels. Fish that can tolerate high CO2 appear to abandon blood pH regulation and instead defend pHi of important tissues, which we have termed preferential pHi (ppHi) regulation. We will investigate the evolution of ppHi regulation, its functional significance and cellular mechanisms and we hypothesize it was associated with the evolution of air-breathing in fish. 3) Teleost fish (half of all vertebrates) possesses a very pH-sensitive haemoglobin (Root effect), where a reduction in pH in specialized structures greatly enhances O2 delivery to the eye and swimbladder which is thought to be associated with the extensive adaptive radiation of teleosts. However, we have discovered a mechanism where a mild acid-base disturbance in the presence of a Root effect can greatly enhance muscle O2 delivery. We will further investigate this mechanism and its' functional significance to determine whether enhanced general O2 delivery may represent the early selection for the Root effect in fish. The proposed experiments are interdisciplinary, spanning the range of molecular, cellular, and whole animal. They are designed to test novel hypotheses and findings will add significantly to our understanding of the evolution of complex physiological systems and have the potential to alter textbook dogma.