Conducted dilation correlates with membrane potential changes in isolated cerebral arterioles. This is an ongoing study.

Ngai, A.C., R.D’Ambrosio, E.F. Coyne, and H.R. Winn. Conducted dilation and membrane potential changes induced by adenosine in rat cerebral arterioles. Soc. Neurosci. Abstr. 27: 2001.

Vasomotor responses, initiated in a distal segment of a vascular network, could spread upstream to the feeding artery that supplies the distal vessel. Such vascular communication obviously exists in the brain, because pial arterioles dilate in response to localized somatosensory activity in the cerebral cortex. Vascular coordination is especially important in the brain, where extraparenchymal arteries and arterioles control over 50% of total vascular resistance. Without the benefit of concomitant upstream response, flow increase by intraparenchymal arteriole dilation alone may not be sufficient for local metabolic needs.

The mechanism underlying vascular communication in the brain has not been concretely elucidated. Our studies suggest that it most likely involves the electrotonic spread of membrane current (depolarization or hyperpolarization) via gap junctions of endothelial and smooth muscle cells.

We conducted studies to measure membrane potential changes in pressurized rat intracerebral arterioles using our in vitro cannulation system. A vasodilating agent (adenosine) was applied to a segment (the local site) of an isolated cerebral arteriole, and changes in the membrane potential changes in a vascular wall cell, as well as the dilation response to adenosine were measured. We next moved the stimulating pipette to a site ~500 mm distant from the local site, and measured the electrical and dilation responses to the remote stimulus (see accompanying figure). Resting membrane potentials were recorded with a glass microelectrode. Pressure-ejection of adenosine elicited local and remote dilations. The conducted dilation was accompanied by hyperpolarization of vascular wall cells in the same remote site. Cells (endothelium or smooth muscle cell) were identified with a fluorescent dye (propidium iodide). Our preliminary results suggest that electrical changes in vascular wall cells mediate the conducted dilation responses of cerebral arterioles to adenosine. The similarity in resting membrane potential and hyperpolarization responses between smooth muscle and endothelial cells moreover suggests electrical coupling between these two cell types.

The involvement of vascular communication in the pathogenesis of ischemic damage and other cerebrovascular diseases is a factor that has often been overlooked. Studies are under way to examine the effect of ischemia/reperfusion on flow-induced and conducted vasomotor responses in cerebral arterioles.

Schematic diagram of a cerebral arteriole showing placement of recording (Em) and adenosine (Ado) application pipettes. Bottom, tracings of membrane potential (Em) and diameter recorded during application of Ado pulse. In this example, Ems were recorded from a smooth muscle cell. Similar responses were seen in endothelial cells. Time mark: 2 s. Constant flow of perfusate (1 ml/min) dissipates the adenosine pulse and prevents it from reaching the recording electrode by diffusion.