Optical imaging of dendritic calcium signals provided evidence of starburst amacrine cells exhibiting calcium bias to somatofugal motion. In contrast, it has been impractical to use a dual-patch clamp technique to record membrane potentials from both proximal dendrites and distal varicosities of starburst amacrine cells in order to unequivocally prove that they are directionally sensitive to voltage, as was first suggested almost two decades ago. This paper aims to extend the passive cable model to an active cable model of a starburst amacrine cell that is intrinsically dependent on the electrical properties of starburst amacrine cells, whose various macroscopic currents are described quantitatively. The coupling between voltage and calcium just below the membrane results in a voltage-calcium system of coupled nonlinear Volterra integral equations whose solutions must be integrated into a prescribed model for example, for a synaptic couplet of starburst amacrine cells. Networks of starburst amacrine cells play a fundamental role in the retinal circuitry underlying directional selectivity. It is suggested that the dendritic plexus of starburst amacrine cells provides the substrate for the property of directional selectivity, while directional selectivity is a property of the exclusive layerings and confinement of their interconnections within the sublaminae of the inner plexiform layer involving cone bipolar cells and directionally selective ganglion cells.
A reaction-diffusion model is presented to encapsulate calcium-induced calcium release (CICR) as a potential mechanism for somatofugal bias of dendritic calcium movement in starburst amacrine cells. Calcium dynamics involves a simple calcium extrusion (pump) and a buffering mechanism of calcium binding proteins homogeneously distributed over the plasma membrane of the endoplasmic reticulum within starburst amacrine cells. The system of reaction-diffusion equations in the excess buffer (or low calcium concentration) approximation are reformulated as a nonlinear Volterra integral equation which is solved analytically via a regular perturbation series expansion in response to calcium feedback from a continuously and uniformly distributed calcium sources. Calculation of luminal calcium diffusion in the absence of buffering enables a wave to travel at distances of 120 μm from the soma to distal tips of a starburst amacrine cell dendrite in 100 msec, yet in the presence of discretely distributed calcium-binding proteins it is unknown whether the propagating calcium wave-front in the somatofugal direction is further impeded by endogenous buffers. If so, this would indicate CICR to be an unlikely mechanism of retinal direction selectivity in starburst amacrine cells.
This study examined the sympathoinhibitory effects of clonidine and a novel clonidine analog, AL-12, in rat models of genetic hypertension and a combined state of genetic hypertension and diabetes. Rats in the treatment groups were given either clonidine or AL-12 while the respective control groups received either saline or Tween 80 for 6 days. Physiological data were collected during this period, which was followed by acute studies on day 7 when bolus administrations (i.v.) of graded doses of noradrenaline, phenylephrine and methoxamine were carried out. It was observed that in AL-12-treated nondiabetic spontaneously hypertensive rats (SHR), the pressure responses to all adrenergic agonists were greater (p < 0.05) in the treated group, while in the diabetic SHR rats a larger pressure response was observed only to noradrenaline (p < 0.05). In nondiabetic SHR rats treated with clonidine, a greater (p < 0.05) pressure response was observed only in the case of phenylephrine. In the diabetic SHR rats treated with clonidine, the pressure responses to the adrenergic agonists were similar (p > 0.05) in the treated and its control animals except that methoxamine caused a greater (p < 0.05) pressure response in the control group. The data obtained suggest that clonidine and AL-12 act possibly via vascular alpha1 and alpha2 adrenoceptors present at both pre- and postsynaptic locations.