Maria del Pilar Gomez, M.D., Ph.D.

Research

Mechanisms of visual excitation and adaptation in photoreceptors

Our laboratory investigates the cellular mechanisms of generation and modulation of the visual response, a prime instance of G protein-mediated signal transduction. We use isolated photoreceptor cells from the unique double retina of marine organisms in which the two main evolutionary lineages of visual cells are represented, microvillar (i.e. 'rhabdomeric') and cilary. Light transduction in these distinct classes of photoreceptors utilizes fundamentally different biochemical cascades to couple photon absorption to the control of the ion channels that give rise to the receptor potential, involving phospholipase C activation and mobilization of cyclic GMP, respectively. Although phototransduction is a specialized function, the same underlying signaling cascades, or elements thereof, operate in a variety of other cells and participate in a host of physiological processes, including the triggering of the immune response, fertilization, and chemoreception. Photoreceptors have served as particularly convenient experimental model systems because of the unusual enrichment of key signaling proteins and the high degree of control that can be easily exerted on the temporal and spatial characteristics of the stimulus.

FIGURE 1 (above): The eye of the scallop, Pecten irradians. A number of these eyes, each <1 mm in diameter, are found along the outer edge of the mantle and possess a single cornea and a lens, similar to vertebrate eyes. Among their remarkable features is the presence of a dual retina, each giving rise to a separate branch of the optic nerve. To form a focused image on the retina, the incoming light is reflected by an interference mirror located at the back of the eye, rather than just refracted by the cornea and the lens.
FIGURE 2: The double retina is composed by two distinct classes of photoreceptors. The cells shown were isolated enzymatically. The light-transducing machinery is located in the microvilli-covered lobe of rhabdomeric cells, and in the modified cilia of ciliary cells, respectively. (s = soma, a = axon stump, r = rhabdomeric lobe, c = ciliary appendages)
	FIGURE 3: Light responses of opposite polarities in the two classes of photoreceptors, recorded by means of whole-cell voltage clamp. Flashes of light of increasing intensity evoke a graded inward ('depolarizing') vs. an outward ('hyperpolarizing') photocurrent. Cell-cell interactions are precluded by dissociating individual photoreceptors.
FIGURE 4: Different transduction cascades are triggered by rhodopsin stimulation in the two types of visual cells. Microvillar photoreceptors utilize a Gq®phosholipase C pathway, which results in the production of IP3 and diacylglycerol (DAG), whereas in ciliary cells light mobilizes cyclic nucleotides. Left: Application of PMA (a phorbol ester DAG analog) to a microvillar photoreceptor activates an inward current that represents a component of the light response. Right: Intracellularly dialysis of a ciliary photoreceptor with a cGMP analog stimulates the light-sensitive outward current.
FIGURE 5: Studies on the dopamine transporter. Neurotransmitter transporters constitute an important class of related proteins, whose major function is the re-uptake of the molecules released upon fusion of synaptic vesicles. In dopaminergic neurons, the dopamine transporter (DAT) has long been implicated in the effects of numerous psychostimulants and substances of abuse, such as amphetamines and cocaine, which induce an accumulation of dopamine (DA) in the extracellular space. The normal transport cycle of DAT is electrogenic and coupled to the concurrent stoichiometric movement of Na and Cl ions, whose electrochemical potential can fuel the translocation of DA against its concentration gradient. This process is reversible, and recent observations have demonstrated that in the Substanbtia nigra of the brain activation of neural inputs can lead to the release of DA, mediated by reverse-mode operation of DAT. Such mechanisms could enable the release of transmitter from non-synaptic regions, a concept of far-reaching implications. In collaboration with Dr. Isabelle Mintz (Nothwestern University), we have recently developed a model system of dissociated dopaminergic neurons from the SN/VTA of the rat, which affords a great degree of experimental control, concomitantly with single-cell detection of released DA. Currently through the use of electrophysiological, immunicytochemical and imaging techniques, we are investigating the determinants of DAT reversal and hope to provide clues on novel mechanisms by which the dopaminergic system is utilized in cell-cell communication, and is targeted by psychostimulant drugs.

Selected Publications:

Gomez, M. and Nasi, E. (1995). Activation of light-dependent potassium channels in ciliary invertebrate photoreceptors involves cGMP but not the IP3/Ca cascade. Neuron. 15: 607-618.

Gomez, M. and Nasi, E. (1997). Antagonists of the cGMP-gated conductance of vertebrate rods block the photocurrent in scallop ciliary photoreceptors. Journal of Physiology. 500: 367-378.

Gomez, M. and Nasi, E. (1998). Membrane current induced by protein kinase C activators in rhabdomeric photoreceptors: implications for visual excitation. Journal of Neuroscience. 18: 5253-5263.

Gomez M. and Nasi, E. (2000). Light transduction in invertebrate hyperpolarizing photoreceptors: possible involvement of a Go-regulated guanylate cyclase. Journal of Neuroscience. 20: 5254-5263.

Piccoli, G., Gomez, M. and Nasi, E. (2002). Role of protein kinase C in light adaptation of microvillar photoreceptors. Journal of Physiology. 543: 481-494.

Gomez, M. and Nasi, E. (2005). Calcium-independent, cGMP-mediated light adaptation in ciliary photoreceptors. Journal of Neuroscience. 25: 2042-2049.

Gomez, M. and Nasi, E. (2005). A direct signalling role for PIP2 in the visual excitation process of microvillar receptors. Journal of Biological Chemistry. 280:16784-16789.

Gomez, M. and Nasi, E. (2005). On the gating mechanism of cGMP-activated channels of hyperpolarizing photoreceptors: does light remove inactivation in voltage-dependent k channels? Journal of General Physiology.125: 455-464.

Complete list of Publications

Contact Us

Department of Physiology and Biophysics
Boston University School of Medicine
700 Albany Street
Boston MA 02118-2526

Phone:(617) 638-4072 • Fax: (617) 638-4273
e-mail: mpgomez@bu.edu