Multiple Second-Messenger System Modulation of Voltage-Activated Calcium Currents in Teleost Retinal Horizontal Cells

Abstract

Two voltage-activated calcium currents, a transient T-type and a PL-sustained type, have been measured in isolated, cultured white bass horizontal cells. These two voltage-activated calcium currents were found to be modulated by two independent second-messenger systems. Furthermore, activation of either second-messenger system led to similar changes in calcium current activity. Activation of the cyclic AMP second-messenger pathway or the sn-1,2-diacylglycerol (DAG) second-messenger system resulted in a significant decrease in the amplitude of the transient current and a simultaneous large increase in the amplitude of the sustained current. Both second-messenger systems achieved their effects through protein phosphorylation. The cyclic AMP pathway resulted in the activation of protein kinase A (PKA) and the DAG pathway worked to activate protein kinase C (PKC). Two protein kinase inhibitors were analyzed in this study for their ability to inhibit second-messenger activated protein kinase activity and separate the two pathways. The peptide cyclic AMP-dependent protein kinase inhibitor and staurosporine were found to be nonspecific at high concentrations and inhibited both second-messenger pathways. At low concentrations however, staurosporine specifically inhibited only PKC, whereas adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor was selective for PKA. Both second-messenger systems were activated by the neuromodulator, dopamine. Thus one agonist can initiate multiple second-messenger systems leading to similar changes in voltage-activated calcium current activity. The modulatory action on calcium currents produced by one second-messenger system added to the modulatory action resulting from activation of the other second-messenger system. The effect is to alter the magnitude of the horizontal cell calcium currents.

Neuromodulation of ligand- and voltage-gated channels in the amphibian retina

“…This suggests that any modification of Ca current may affect the horizontal cell responses to the light stimuli. Modulation of Ca currents in retinal horizontal cells by dopamine and glutamate has been reported earlier (Linn and Gafka, 1999;Pfeiffer-Linn and Lasater, 1998).…”

Photic regulation of heme oxygenase activity in the golden hamster retina: involvement of dopamine

“…Whether the effect of PKA activation on the increase in HO‐2 activity is direct or, alternatively, it involves a cross‐talk with other signaling pathways (such as PKC) is under current investigation. In fact, some retinal effects of dopamine involve both PKA and PKC signaling pathways (Rodrigues Pdos and Dowling 1990; Simpson and Morris 1995; Pfeiffer‐Linn and Lasater 1998). In a previous report, we demonstrated that retinal NOS activity is also regulated by the photic signal but in an opposite way to that shown herein for HO‐2 activity (Llomovatte et al .…”

Intracellular calcium release resulting from mGluR1 receptor activation modulates GABAA currents in wide‐field retinal amacrine cells: a study with caffeine

“…The cell isolation procedure followed is similar to that previously described in detail (Pfeiffer‐Linn & Lasater, 1998). Briefly, white bass ( Morone chrysops ) were dark‐adapted for 2 h and then killed by cervical transection in accordance with the Association for Research in Vision and Ophthalmology guidelines.…”