HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 93/3/1468    most recent 00874.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Cia, D. Articles by Picaud, S. Search for Related Content PubMed PubMed Citation Articles by Cia, D. Articles by Picaud, S.

Voltage-Gated Channels and Calcium Homeostasis in Mammalian Rod Photoreceptors

¹Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine, Institut National de la Santé et de la Recherche Médicale U-592, Université Pierre et Marie Curie; ²Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts; and ³Fondation Ophtalmologique Adolphe de Rothschild, Paris, France

Submitted 24 August 2004; accepted in final form 5 October 2004

Recent reports on rod photoreceptor neuroprotection by Ca²⁺ channel blockers have pointed out the need to assess the effect of these blockers on mammalian rods. However, in mammals, rod electrophysiological characterization has been hampered by the small size of these photoreceptors, which were instead extensively studied in nonmammalian vertebrates. To further characterize ionic conductances and to assess the pharmacology of Ca²⁺ channels in mammalian rods, freshly dissociated pig rod photoreceptors were recorded with the whole cell patch-clamp technique. Rod cells expressed 1) a hyperpolarization-activated inward-rectifying conductance (I_h) sensitive to external Cs⁺; 2) a sustained outward K⁺ current (I_K) sensitive to tetraethylammonium; 3) a sustained voltage-gated Ca²⁺ current (I_Ca) sensitive to benzothiazepine (diltiazem) and phenylalkylamine (verapamil) derivatives; 4) a Ca²⁺-activated Cl^– current (I_Cl(Ca)); and 5) a plasma membrane Ca²⁺-ATPase. The Ca²⁺ current showed a range of activation from positive potentials to –60 mV with a maximum between –30 and –20 mV. In contrast to other L-type Ca²⁺ channels, rod Ca²⁺ channels were blocked at similar and relatively high concentrations by the diltiazem isomers and verapamil. The biphasic dose-response for D-diltiazem confirmed the low sensitivity of Ca²⁺ channels for the molecule. The ATPase, which was localized at the axon terminal, was found to contribute to Ca²⁺ extrusion. These results suggest that the electrophysiological features of rod photoreceptors had been preserved during evolution from nonmammalian vertebrates to mammals. This work indicates further that mammalian rods express nonclassic L-type Ca²⁺ channels, showing a low sensitivity to the diltiazem isomers used in neuroprotective studies.