Regulation of voltage-sensitive Ca2+ channels in bipolar cells by divalent cations and polyamines

Ca2+ plays a key role in intracellular signal transduction in neurons but in excess it can lead to cell death. Thus its entry into cells is highly regulated by both extrinsic and intrinsic mechanisms. Little is known of the regulation of Ca2+ entry into retinal neurons. Here we describe the role of divalent cations and polyamines as intrinsic modulators of Ca2+ entry into retinal bipolar cells. Cone-dominant (small) bipolar cells of the white bass retina were studied using whole cell patch clamp techniques. With biophysical and pharmacological tools it was determined that these cells expressed a Ca2+ current similar to an L-type current. This current was very susceptible to blockage by divalent cations including Ca2+. In addition, when tested with the polyamines, spermine, spermidine and putrescine, only spermine effectively inhibited the current. When the dose response curve was fit with the Hill function we found an EC50 of 28 muM and a Hill-coefficient of about 2. Our results indicate that divalent cations and the polyamine, spermine, are effective modulators of calcium entry into cone-dominated bipolar cells. The in vivo regulation of the concentrations of these molecules provides an exquisitely sensitive mechanism for regulating Ca2+ entry into bipolar cells under different conditions.