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鱼类在环境适应/适应和发育过程中气体交换、离子调节和酸碱平衡之间的相互作用。在这项提案中，我将调查三个与酸碱调节相互作用的领域，作为一个共同的主题，重点主要是“原始”和发展鱼类。1)鱼鳃是多功能的，由气体交换、离子调节和酸碱平衡的主要表面组成，所有这些过程对生存都至关重要。总的来说，脊椎动物的鳃被认为主要是为了加强气体交换而进化的，其次是为了其他过程，然而，根据我们最近的发现，我们假设脊椎动物的鳃首先进化为酸碱调节，其次是气体交换。2)虽然鳃是鱼类血液pH调节的主要部位，但在高二氧化碳水平下，它们的这一能力变得有限。能耐受高二氧化碳的鱼类似乎放弃了血液pH调节，转而防御重要组织的phi，我们称之为优先phi(PpHi)调节。我们将研究ppHi调节的进化，它的功能意义和细胞机制，我们假设它与鱼类呼吸空气的进化有关。3)硬骨鱼(所有脊椎动物的一半)具有对pH非常敏感的血红蛋白(根效应)，其特殊结构中pH的降低极大地增加了向眼睛和鱼囊的氧气输送，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，在根效应存在的情况下，轻微的酸碱失衡可以极大地增强肌肉的氧气输送。我们将进一步研究这一机制及其功能意义，以确定增强的一般氧气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上的教条。

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.