An extracellular signaling component in propagation of astrocytic calcium waves

Focally evoked calcium waves in astrocyte cultures have been thought to propagate by gap-junction-mediated intercellular passage of chemical signal(s). In contrast to this mechanism we observed isolated astrocytes, which had no physical contact with other astrocytes in the culture, participating in a calcium wave. This observation requires an extracellular route of astrocyte signaling. To directly test for extracellular signaling we made cell-free lanes 10–300 μm wide in confluent cultures by deleting astrocytes with a glass pipette. After 4–8 hr of recovery, regions of confluent astrocytes separated by lanes devoid of cells were easily located. Electrical stimulation was used to initiate calcium waves. Waves crossed narrow (<120 μm) cell-free lanes in 15 of 36 cases, but failed to cross lanes wider than 120 μm in eight of eight cases. The probability of crossing narrow lanes was not correlated with the distance from the stimulation site, suggesting that cells along the path of the calcium wave release the extracellular messenger(s). Calculated velocity across the acellular lanes was not significantly different from velocity through regions of confluent astrocytes. Focal superfusion altered both the extent and the direction of calcium waves in confluent regions. These data indicate that extracellular signals may play a role in astrocyte–astrocyte communication in situ.

Fire–diffuse–fire model of dynamics of intracellular calcium waves

When Ca2+ is released from internal stores in living cells, the resulting wave of increased concentration can travel without deformation (continuous propagation) or with burst-like behavior (saltatory propagation). We analyze the “fire–diffuse–fire” model in order to illuminate the differences between these two modes of propagation. We show that the Ca2+ release wave in immature Xenopus oocytes and cardiac myocytes is saltatory, whereas the fertilization wave in the mature oocyte is continuous.

Selection for spiral waves in the social amoebae Dictyostelium

Starving Dictyostelium amoebae emit pulses of the chemoattractant cAMP that are relayed from cell to cell as circular and spiral waves. We have recently modeled spiral wave formation in Dictyostelium. Our model suggests that a secreted protein inhibitor of an extracellular cAMP phosphodiesterase selects for spirals. Herein we test the essential features of this prediction by comparing wave propagation in wild type and inhibitor mutants. We find that mutants rarely form spirals. The territory size of mutant strains is approximately 50 times smaller than wild type, and the mature fruiting bodies are smaller but otherwise normal. These results identify a mechanism for selecting one wave symmetry over another in an excitable system and suggest that the phosphodiesterase inhibitor may be under selection because it helps regulate territory size.

Active control of waves in a cochlear model with subpartitions.

Multiscale asymptotic methods developed previously to study macromechanical wave propagation in cochlear models are generalized here to include active control of a cochlear partition having three subpartitions, the basilar membrane, the reticular lamina, and the tectorial membrane. Activation of outer hair cells by stereocilia displacement and/or by lateral wall stretching result in a frequency-dependent force acting between the reticular lamina and basilar membrane. Wavelength-dependent fluid loads are estimated by using the unsteady Stokes' equations, except in the narrow gap between the tectorial membrane and reticular lamina, where lubrication theory is appropriate. The local wavenumber and subpartition amplitude ratios are determined from the zeroth order equations of motion. A solvability relation for the first order equations of motion determines the subpartition amplitudes. The main findings are as follows: The reticular lamina and tectorial membrane move in unison with essentially no squeezing of the gap; an active force level consistent with measurements on isolated outer hair cells can provide a 35-dB amplification and sharpening of subpartition waveforms by delaying dissipation and allowing a greater structural resonance to occur before the wave is cut off; however, previously postulated activity mechanisms for single partition models cannot achieve sharp enough tuning in subpartitioned models.