Institut de Biologie de l'École Normale Supérieure, Paris, France.
Department of Integrative Biology and Physiology, University of California, Los Angeles, California, USA.
J Physiol. 2021 Jul;599(13):3295-3312. doi: 10.1113/JP281225. Epub 2021 Jun 8.
Most vertebrate eyes have rod and cone photoreceptors, which use a signal transduction pathway consisting of many biological processes to transform light into an electrical response. We dissect and quantify the contribution of each of these processes to the photoreceptor light response by using a novel method of analysis that provides an analytical solution for the entire time course of the dim-flash light response. We find that the shape of the light response is exclusively controlled by deactivation parameters. Activation parameters scale this shape and alter the response amplitude. We show that the rising phase of the response depends on Ca feedback, and we identify the deactivation parameters that control the recovery phase of the response. We devise new methods to extract values for deactivation and activation parameters from a separate analysis of response shape and response amplitude.
Vertebrate eyes have rod and cone photoreceptors, which use a complex transduction pathway comprising many biological processes to transform the absorption of light into an electrical response. A fundamental question in sensory transduction is how these processes contribute to the response. To study this question, we use a well-accepted phototransduction model, which we analyse with a novel method based on the log transform of the current. We derive an analytical solution that describes the entire time course of the photoreceptor response to dim flashes of light. We use this solution to dissect and quantify the contribution of each process to the response. We find that the entire dim-flash response is proportional to the flash intensity. By normalizing responses to unit amplitude, we define a waveform that is independent of the light intensity and characterizes the invariant shape of dim-flash responses. We show that this waveform is exclusively determined by deactivation rates; activation rates only scale the waveform and affect the amplitude. This analysis corrects a previous assumption that the rising phase is determined entirely by activation rates. We further show that the rising phase depends on Ca feedback to the cyclase, contrary to current belief. We identify the deactivation rates that control the recovery phase of the response, and we devise new methods to extract activation and deactivation rates from an analysis of response shape and response amplitude. In summary, we provide a comprehensive understanding of how the various transduction processes produce the cellular response.
大多数脊椎动物的眼睛都有视杆和视锥感光细胞，它们利用包含许多生物过程的信号转导途径将光转化为电响应。我们通过一种新的分析方法来剖析和量化这些过程中的每一个过程对光感受器光响应的贡献，该方法提供了整个暗闪光光响应过程的解析解。我们发现，光响应的形状仅由去激活参数控制。激活参数则对这种形状进行缩放，并改变响应幅度。我们表明，响应的上升阶段取决于 Ca 反馈，我们确定了控制响应恢复阶段的去激活参数。我们设计了新的方法，从对响应形状和响应幅度的单独分析中提取去激活和激活参数的值。
脊椎动物的眼睛有视杆和视锥感光细胞，它们利用包含许多生物过程的复杂转导途径将光的吸收转化为电响应。在感觉转导中，一个基本问题是这些过程如何共同促成响应。为了研究这个问题，我们使用了一个广为人接受的光转导模型，并用一种基于电流对数变换的新方法对其进行分析。我们得出了一个描述光感受器对弱光闪光的整个时间过程的解析解。我们利用该解来剖析和量化每个过程对响应的贡献。我们发现，整个弱闪光响应与闪光强度成正比。通过将响应归一化为单位幅度，我们定义了一个与光强度无关且表征弱闪光响应不变形状的波形。我们表明，这个波形完全由去激活速率决定；激活速率仅对波形进行缩放，并影响幅度。这种分析纠正了以前的假设，即上升阶段完全由激活速率决定。我们进一步表明，与目前的观点相反，上升阶段取决于对环化酶的 Ca 反馈。我们确定了控制响应恢复阶段的去激活速率，并设计了新的方法，从对响应形状和响应幅度的分析中提取激活和去激活速率。总之，我们提供了对各种转导过程如何产生细胞响应的全面理解。
