Antagonists of the cGMP-gated conductance of vertebrate rods block the photocurrent in scallop ciliary photoreceptors.
1. Hyperpolarizing scallop photoreceptors, like vertebrate rods, use cGMP as an internal messenger and their light-sensing structure is also of ciliary origin. To ascertain possible functional similarities between the light-sensitive conductances in the two classes of visual cells, we examined in scallop photoreceptors the effects of several antagonists of the photocurrent of rods. 2. Extracellular application of L-cis-diltiazem rapidly and reversibly suppressed the photocurrent. The effect was stereospecific and dose dependent, with a K1/2 of approximately 400 microM. Intracellular dialysis at lower doses (100-200 microM) also induced a substantial inhibition. 3. L-cis-Diltiazem reduced the light-activated conductance without shifting the intensity-response curve. Furthermore, the drug also blocked the current directly evoked by application of cGMP. These observations indicate that the inhibitory effects result from blockage of the conductance, rather than from impairment of the activating cascade. 4. The fractional blockage increased e-fold per approximately 55 mV depolarization, regardless of the side of drug application, as if the charged form of L-cis-diltiazem can only access the blocking site from the intracellular compartment. 5. The amiloride derivative 3',4'-dichlorobenzamil potently suppressed the photocurrent (K1/2 approximately 5 microM), without affecting its kinetics or operating range. Amiloride itself was also effective at higher concentrations. 6. The pharmacological resemblance of these light-dependent channels to those of rods and cones indicates that significant aspects of the transduction cascade are conserved across disparate sensory cells of ciliary origin.
Gomez
M P
MP
Department of Physiology, Boston University School of Medicine, MA 02118, USA.
Nasi
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D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008974:Mollusca; D018408:Patch-Clamp Techniques; D017956:Photoreceptor Cells, Invertebrate / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; C041470:3',4'-dichlorobenzamil; C016276:8-bromocyclic GMP; D000584:Amiloride; D004110:Diltiazem; D006152:Cyclic GMP