Evidence for K⁺ channels involvement in capillary sensing and for bidirectionality in capillary communication

Although the capillary sensing and communication phenomenon has been characterized, its mechanism is not clear. It has been hypothesized that capillary sensing involves a membrane potential change in the capillary endothelium and/or pericyte and that communication represents an electrotonic spread of this change along the capillary. The goal of the present study was to address this hypothesis by examining the presence of K⁺ channels on the capillary and by determining bidirectionality of communication. Using intravital microscopy, we locally applied K⁺ (100 mM), acetylcholine (ACh; 3 mM), and norepinephrine (NE; 0.3 mM) on capillaries, 400-500 μm downstream from the arteriole, at the surface of the sartorius muscle in anesthetized frogs. Responses were measured in terms of red blood cell velocity (V(RBC)) changes in the stimulated capillary (control prestimulation V(RBC) ranged from 110 to 770 μm/sec). K⁺ and ACh caused significant 19 and 38% increases in V(RBC), while NE caused a -46% decrease, respectively. The K⁺ response was blocked by local pretreatment with K⁺ channel blocker BaCl₂ (1 μM) and by pretreatment with tetraethyl ammonium chloride (TEA; 5 mM). Responses to ACh and NE were attenuated by pretreatment with 1 μM BaCl₂ (to 1%) and with 50 mM TEA (to -25%), respectively. In a separate experiment, NE (3 mM) application on the capillary 500 μm away from the draining venule (capillary occluded) caused a 19% venular constriction (i.e., similar to a reported 21% arteriolar constriction caused by the NE stimulus). We concluded that (i) K⁺ channels were present on the capillary and (ii) capillary communication was bidirectional. We interpreted these results to be consistent with the above hypothesis of membrane potential change and electrotonic spread.