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J Neurophysiol 80: 377-388, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 80 No. 1 July 1998, pp. 377-388
Copyright ©1998 The American Physiological Society

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

Cindy L. Pfeiffer-Linn and Eric M. Lasater

John Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah 84132

Pfeiffer-Linn, Cindy L. and Eric M. Lasater. Multiple second-messenger system modulation of voltage-activated calcium currents in teleost retinal horizontal cells. J. Neurophysiol. 80: 377-388, 1998. 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.




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J. Vigh, E. Solessio, C. W. Morgans, and E. M. Lasater
Ionic Mechanisms Mediating Oscillatory Membrane Potentials in Wide-Field Retinal Amacrine Cells
J Neurophysiol, July 1, 2003; 90(1): 431 - 443.
[Abstract] [Full Text] [PDF]


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