Question: 

The myogenic response, one of the most powerful mechanisms of blood flow autoregulation, is controlled by a balance of contractile and dilatory mechanisms, the latter being dominated by voltage-gated potassium (Kv1) channels. However, experimental evidence supporting this conclusion was obtained using non-pulsatile pressure, despite pulsatile pressure being the physiological stimulus. Thus, the component of pulsatile pressure (systolic, mean, diastolic) controlling the myogenic response and the role of Kv1 channels in determining the controlling component is unknown. Therefore, the hypothesis was tested that pulsatile pressure has a specific effect on the myogenic response of rat small arteries and that Kv1 channels contribute critically to this effect.

Methodology: 

Experiments were performed on rat small superior cerebellar arteries studying Kv1 channel expression using real time PCR, Kv1 currents using the patch clamp technique and the myogenic response using isobaric myography.

Results: 

mRNA-expression of some Kv1-family members was detected in whole vessel homogenates with the expression level of Kv1.5>>Kv1.3>Kv1.2>Kv1.6. In isolated smooth muscle cells, the Kv1 channel inhibitor DPO-1 reduced Kv currents by 59% at saturating concentrations (EC₅₀ 200nmol/L). DPO-1 constricted intact vessels in a concentration-dependent manner between 0.01–1mmol/L. Myogenic tone induced by non-pulsatile pressure in the range between 40 and 120 mmHg was enhanced in the presence of 0.3mmol/L DPO-1. Vessels were exposed to pulsatile pressure with a mean pressure adjusted to the level of the control non-pulsatile pressure. Myogenic tone induced by pulsatile pressure was weaker than tone induced by non-pulsatile pressure over the whole pressure range studied. In contrast, in the presence of 0.3mmol/L DPO-1, myogenic tone was the same in the presence of pulsatile as well as non-pulsatile pressure.

Conclusion: 

Our study demonstrates that in rat superior cerebellar arteries (i) Kv1.5 channels are the predominantly expressed smooth muscle Kv1 channel, (ii) the myogenic response is determined by the diastolic component of pulsatile pressure and (iii) Kv1.5 channels are necessary for diastolic blood pressure to control myogenic tone.