The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.
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Ionic Mechanisms in Mouse Rod Photoreceptor Signaling

Frans Vinberg

Doctoral dissertation for the degree of Doctor of Science in Technology to be presented with due permission of the School of Science for public examination and debate in Auditorium F239 at the Aalto University School of Science (Espoo, Finland) on the 21st of September 2011 at 12 noon.

Overview in PDF format (ISBN 978-952-60-4235-0)   [999 KB]
Dissertation is also available in print (ISBN 978-952-60-4234-3)

Abstract

Photoreceptor cells are an example of biological transducer devices: they transform photon energy into an electrical signal and transmit it to higher-order neurons. Vertebrate photoreceptor cells can be categorized into two classes, rods and cones. The rod photoreceptors are extremely sensitive to light, whereas cones are faster than rods and can function under bright ambient illumination. The rod photoreceptor cell is a convenient model for studying modulation of physiological transduction and transmission processes because 1) the rod's natural input signal, light, can be applied quantitatively and 2) the absorption of only one or a few photons by the visual pigment molecules in the cell's outer segment is transformed into a measurable change of the rod's membrane potential (Vm). The gain of the photon-to-Vm conversion in rods is rapidly (in a fraction of a second) modulated by several ionic feedback mechanisms. The mechanisms involved in rod signal generation and feedback signaling were investigated in the present work by recording rods' electrical responses to light stimuli from intact mouse retinas with transretinal electroretinogram (ex vivo ERG).

Several negative feedback mechanisms that accelerate a rod's response recovery after light stimuli rely on the light-induced decline in the calcium ion (Ca2+) concentration in the rod outer segment. Further, some voltage- and Ca2+ -dependent mechanisms in the rod inner segment plasma membrane modulate the gain of the photon-to-Vm conversion. In this thesis the specificity of the known Ca2+ signaling mechanisms, and Ca2+ dependency of the reaction that rate-limits the rod's recovery after bright stimuli were investigated. It was found that the transition metal ion Co2+ can mediate the known Ca2+ dependent negative feedback mechanisms in the rod outer segment, and that a certain minimum amount of Ca2+ is necessary in setting the physiological value of the speed of the rate-limiting recovery reaction. The role of the inner segment ionic channels in generating the rod ERG response was also elucidated. It was shown that the hyperpolarization activated (h) channels in the rod inner segment participate in the generation of a fast transient component that is evident in the rod ERG response to bright flashes. Instead, voltage-dependent Ca2+ channels or Ca2+ -activated potassium and chloride currents did not contribute to that component. Additionally, modulation of the direct electrical transmission between rods and cones was studied. The present work suggests that the electrical connection between rods and cones can be closed by light in the mouse retina.

This thesis consists of an overview and of the following 4 publications:

  1. Frans J. Vinberg, Satu Strandman, and Ari Koskelainen. 2009. Origin of the fast negative ERG component from isolated aspartate-treated mouse retina. Journal of Vision, volume 9, number 12, article 9, 17 pages.
  2. Frans Vinberg and Ari Koskelainen. 2010. Calcium sets the physiological value of the dominant time constant of saturated mouse rod photoresponse recovery. PLoS ONE, volume 5, number 9, article e13025, 12 pages. © 2010 by authors.
  3. Frans Vinberg and Ari Koskelainen. 2011. Cobalt (Co2+) can mediate dynamic feedback signals driven by calcium (Ca2+) sensor molecules in mouse rod photoreceptors. Research report. Espoo, Finland: Aalto University, School of Science, Department of Biomedical Engineering and Computational Science. 28 pages. Aalto University publication series SCIENCE + TECHNOLOGY 12/2011. Aalto-ST-12/2011. ISBN 978-952-60-4164-3. ISSN 1799-490X. © 2011 by authors.
  4. H. Heikkinen, F. Vinberg, S. Nymark, and A. Koskelainen. 2011. Mesopic background lights enhance dark-adapted cone ERG flash responses in the intact mouse retina: a possible role for gap junctional decoupling. Journal of Neurophysiology, volume 105, number 5, pages 2309-2318. © 2011 American Physiological Society (APS). By permission.

Keywords: photoreceptor, electrophysiology, electroretinogram, calcium signaling

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© 2011 Aalto University

Last update 2012-07-12