Minor role of a Ca2+-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K+

Exposure ofporcine carotid artery smooth muscle (PCASM) to histamine was followedby a large reduction in the rate of force generation in response to 40 mM KCl. This was shown to be a manifestation of slow attainment of asteady-state myoplasmic Ca²⁺concentration(Ca²⁺]_i).We hypothesized that if net transsarcolemmalCa²⁺ flux into the depolarizedPCASM cells is the same before and after a desensitizing histaminetreatment, then the transient attenuation of the increase inCa²⁺]_imay be due to accelerated uptake ofCa²⁺ by a partially depletedsarcoplasmic reticulum (SR) acting as aCa²⁺ sink or superficial bufferbarrier. We tested this hypothesis by eliciting responses of"desensitized PCASM" to 40 mM KCl in the presence ofcyclopiazonic acid (CPA), an SRCa²⁺-ATPase inhibitor.Contractions of CPA-treated tissues were attenuated less than those oftissues not treated with CPA, but they were not abolished.CPA-insensitive mechanism(s) dominated the desensitization. We concludethat histamine pretreatment reduced net transsarcolemmal Ca²⁺ flux into PCASM in responseto 40 mM KCl.